bigbio/osiris · Datasets at Hugging Face

id stringlengths 1 3	document_id stringlengths 8 8	passages list	entities list	events list	coreferences list	relations list
101	15150650	[ { "id": "fc75aa4a-caba-4f68-a13a-325f9117cdec", "type": "title", "text": [ "The allelic variant of LAR gene promoter -127 bp T-->A is associated with reduced risk of obesity and other features related to insulin resistance." ], "offsets": [ [ 0, 153 ] ] }, { "id": "c5abebc1-28c4-4b1b-b1b8-6addad3944d4", "type": "abstract", "text": [ "Insulin resistance, which is pathogenic for type 2 diabetes (T2D), is under the control of largely unknown genetic determinants. LAR , a protein-tyrosine phosphatase which inhibits insulin signalling, is overexpressed in animal and human models of insulin resistance. We studied the entire sequence of the LAR gene by SSCP analysis and automatic DNA sequencing, with the aim of verifying whether its sequence variants might be associated with insulin resistance. In the 276 bp sequence upstream of the transcriptional start site (i.e. a region we have identified as having basal promoter activity) a -127 bp T-->A SNP (5% frequency) was associated with lower body mass index (BMI) ( P=0.03), waist circumference ( P=0.01), blood pressure ( P=0.01) and urinary albumin/creatinine ratio ( P=0.04) in 589 non-diabetic unrelated individuals from the Gargano region (central east coast of Italy). To quantify the risk for a high body weight conferred by the -127 T-->A SNP, the whole cohort was divided into tertiles according to the individual BMI. The risk of belonging to the heavier tertile, as compared to the leaner one, was reduced by approximately 60%. In a population from East Sicily ( n=307), T/A genotype carriers ( n=13) showed lower triglyceride levels ( P=0.04) and higher insulin sensitivity as indicated by lower plasma glucose ( P=0.03) and serum insulin ( P=0.006) during oral glucose tolerance testing (OGTT). Promoter activity, studied by cDNA transfection experiments, was similar for the A and T alleles. In conclusion, a genetic variant of the LAR gene promoter is consistently associated with features of insulin resistance in two different Caucasian populations. Although the biological relevance of this variant has yet to be determined, this finding underlines the potential importance of the LAR gene in dysregulation of insulin sensitivity and related disorders." ], "offsets": [ [ 154, 2067 ] ] } ]	[ { "id": "3153d8a4-4361-4ffc-8fb0-89553ee6119a", "type": "gene", "text": [ "Insulin" ], "offsets": [ [ 154, 161 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "3630" } ] }, { "id": "c21f43a0-db80-4cb9-9b76-b13cf6a290e8", "type": "gene", "text": [ "LAR" ], "offsets": [ [ 24, 27 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "5792" } ] }, { "id": "06772945-bf4e-4382-95ef-3835c4faafa5", "type": "gene", "text": [ "insulin" ], "offsets": [ [ 133, 140 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "3630" } ] }, { "id": "817f2145-ebaa-4051-b769-4e5763e5a563", "type": "gene", "text": [ "insulin" ], "offsets": [ [ 133, 140 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "3630" } ] }, { "id": "a445999b-017b-4403-a48c-a6e1bc1287f0", "type": "gene", "text": [ "LAR" ], "offsets": [ [ 24, 27 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "5792" } ] }, { "id": "83786043-e198-4d07-bf11-05d876c79185", "type": "gene", "text": [ "insulin" ], "offsets": [ [ 133, 140 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "3630" } ] }, { "id": "6e109683-485c-414d-8683-685b5d3196b6", "type": "gene", "text": [ "insulin" ], "offsets": [ [ 133, 140 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "3630" } ] }, { "id": "d6e04615-5e4c-4d68-8682-525c4c288c34", "type": "gene", "text": [ "insulin" ], "offsets": [ [ 133, 140 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "3630" } ] }, { "id": "d1d8c084-ec05-4eaf-bc85-63b47ef3fabe", "type": "gene", "text": [ "LAR" ], "offsets": [ [ 24, 27 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "5792" } ] }, { "id": "c7ee4786-b5d7-40cf-876b-0ac27a0a3d43", "type": "gene", "text": [ "insulin" ], "offsets": [ [ 133, 140 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "3630" } ] }, { "id": "5521f810-6072-471d-885c-cbf08899d24e", "type": "gene", "text": [ "LAR" ], "offsets": [ [ 24, 27 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "5792" } ] }, { "id": "351e5e8b-b5be-480b-9870-46f5a66e0870", "type": "gene", "text": [ "insulin" ], "offsets": [ [ 133, 140 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "3630" } ] }, { "id": "df734e6e-b723-476a-a3d1-1896d92d4b44", "type": "variant", "text": [ "-127 bp T-->A" ], "offsets": [ [ 44, 57 ] ], "normalized": [ { "db_name": "dbSNP", "db_id": "3001722" } ] }, { "id": "81a361d8-a925-4487-9a96-0b2715006d79", "type": "variant", "text": [ "-127 T-->A" ], "offsets": [ [ 1120, 1130 ] ], "normalized": [ { "db_name": "dbSNP", "db_id": "3001722" } ] } ]	[]	[]	[]
102	15161528	[ { "id": "1f68e7de-096b-4068-b87a-df10c157d752", "type": "title", "text": [ "Single nucleotide polymorphisms of the SCN5A gene in Han Chinese and their relation with Brugada syndrome." ], "offsets": [ [ 0, 108 ] ] }, { "id": "68872a56-83a9-4162-be79-dc0b42e466c7", "type": "abstract", "text": [ "BACKGROUND: Mutations in the cardiac sodium channel gene ( SCN5A ) may lead to a broad spectrum of familial arrhythmias, including long QT syndrome (LQTS), idiopathic ventricular fibrillation (IVF), and isolated cardiac conduction diseases. Recent studies have shown that polymorphisms in the SCN5A gene also play an important role in the manifestation of disorders involving cardiac excitability. In this study, we investigated the polymorphisms of the SCN5A gene in Han Chinese and its relation to Brugada syndrome (BS). METHODS: Genomic DNA was isolated from 120 unrelated healthy volunteers and 48 unrelated Brugada syndrome patients by means of standard procedures. All exons including the putative splicing sites of the SCN5A gene were amplified by PCR and sequenced directly or after subcloning using an ABI Prism 377 DNA sequencer. RESULTS: A total of 5 single nucleotide polymorphisms (SNPs) were identified in the Han Chinese population, including 3 novel ones: G87A (A29A) , 4245 + 82A > G , and G6174A . The allele frequencies of each SNP in the Han Chinese population were as follows: G87A (A29A) 27.5%, A1673G (H558R) 10.4%, 4245 + 82A > G 32.8%, C5457T (D1819D) 41.3%, and G6174A 44.9%. S1102Y and 10 other SNPs identified in other ethnic populations were not detected in this study. There was no significant difference in the allele frequency of A1673G (H558R) between different ethnic populations (all P > 0.5). On the other hand, the allele frequency of C5457T (D1819D) among Han Chinese was similar to its frequency among Japanese (P > 0.5), but higher than that among Americans (P < 0.005). The allele G1673 (R558) was over-represented in BS patients compared to controls (P < 0.005), but there was no significant difference in genotype frequencies at this locus. There were also no differences in either the allele or genotype frequencies of the 4 other identified SNPs when comparing BS patients with healthy controls. CONCLUSIONS: The distribution of SCN5A SNPs may vary between different ethnicities. The polymorphism of A1673G might be associated with BS and may contribute to a susceptibility to BS in Han Chinese." ], "offsets": [ [ 109, 2300 ] ] } ]	[ { "id": "942203bc-1533-49fc-9227-199c383e2162", "type": "gene", "text": [ "cardiac sodium channel gene" ], "offsets": [ [ 139, 166 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "6331" } ] }, { "id": "cad0b594-47c7-4765-9722-93800e3d1fb4", "type": "gene", "text": [ "SCN5A" ], "offsets": [ [ 40, 45 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "6331" } ] }, { "id": "4b138e56-7ad7-468c-84d8-7c95c70661de", "type": "gene", "text": [ "SCN5A" ], "offsets": [ [ 40, 45 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "6331" } ] }, { "id": "bcb70aa8-df10-4972-a478-c5e4465443df", "type": "gene", "text": [ "SCN5A" ], "offsets": [ [ 40, 45 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "6331" } ] }, { "id": "6493f585-b971-46e5-a39a-44a28e912a59", "type": "gene", "text": [ "SCN5A" ], "offsets": [ [ 40, 45 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "6331" } ] }, { "id": "bd0a5f45-6401-4eb4-b129-ce20bb3ae385", "type": "gene", "text": [ "SCN5A" ], "offsets": [ [ 40, 45 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "6331" } ] }, { "id": "f8a4ad84-d64b-4dc4-a99c-c10d98bba00e", "type": "variant", "text": [ "G87A" ], "offsets": [ [ 1090, 1094 ] ], "normalized": [ { "db_name": "dbSNP", "db_id": "6599230" } ] }, { "id": "9b732b5c-2359-4b54-892d-1b17a5880130", "type": "variant", "text": [ "(A29A)" ], "offsets": [ [ 1097, 1103 ] ], "normalized": [ { "db_name": "dbSNP", "db_id": "6599230" } ] }, { "id": "c8e19412-6709-414d-bf3a-8bfefb72c94d", "type": "variant", "text": [ "4245 + 82A > G" ], "offsets": [ [ 1107, 1121 ] ], "normalized": [ { "db_name": "HGVS-like", "db_id": "A82G" } ] }, { "id": "61b4edf1-d937-4348-8135-85168cda498d", "type": "variant", "text": [ "G6174A" ], "offsets": [ [ 1129, 1135 ] ], "normalized": [ { "db_name": "HGVS-like", "db_id": "G6174A" } ] }, { "id": "e3a0c63c-8f6c-4d7a-8025-101db6989e41", "type": "variant", "text": [ "G87A" ], "offsets": [ [ 1090, 1094 ] ], "normalized": [ { "db_name": "dbSNP", "db_id": "6599230" } ] }, { "id": "2195feb1-9762-413f-9aa9-b0450b2eec69", "type": "variant", "text": [ "(A29A)" ], "offsets": [ [ 1097, 1103 ] ], "normalized": [ { "db_name": "dbSNP", "db_id": "6599230" } ] }, { "id": "186c6d2a-9b7b-4f5c-ac56-84360f79e6f9", "type": "variant", "text": [ "A1673G " ], "offsets": [ [ 1244, 1251 ] ], "normalized": [ { "db_name": "dbSNP", "db_id": "1805124" } ] }, { "id": "a8695a12-c7ee-431b-83eb-ee9865bec933", "type": "variant", "text": [ "(H558R) " ], "offsets": [ [ 1254, 1262 ] ], "normalized": [ { "db_name": "dbSNP", "db_id": "1805124" } ] }, { "id": "5f397eb0-e2df-450e-9325-0484d7696045", "type": "variant", "text": [ "4245 + 82A > G" ], "offsets": [ [ 1107, 1121 ] ], "normalized": [ { "db_name": "HGVS-like", "db_id": "A82G" } ] }, { "id": "9ca82397-b598-4667-93b2-cd6ebc00e21c", "type": "variant", "text": [ "C5457T " ], "offsets": [ [ 1295, 1302 ] ], "normalized": [ { "db_name": "dbSNP", "db_id": "1805126" } ] }, { "id": "0c925751-a6ab-498f-b206-cd8046ece86c", "type": "variant", "text": [ "(D1819D) " ], "offsets": [ [ 1305, 1314 ] ], "normalized": [ { "db_name": "dbSNP", "db_id": "1805126" } ] }, { "id": "a6f89dc3-d7c9-4ff4-b824-2e479ca256a5", "type": "variant", "text": [ "G6174A" ], "offsets": [ [ 1129, 1135 ] ], "normalized": [ { "db_name": "HGVS-like", "db_id": "G6174A" } ] }, { "id": "8e44bc70-72d9-4e60-a5c0-350301d1639d", "type": "variant", "text": [ "S1102Y" ], "offsets": [ [ 1343, 1349 ] ], "normalized": [ { "db_name": "dbSNP", "db_id": "7626962" } ] }, { "id": "a706a7e5-7873-424d-b6fa-8325910ba173", "type": "variant", "text": [ "A1673G " ], "offsets": [ [ 1244, 1251 ] ], "normalized": [ { "db_name": "dbSNP", "db_id": "1805124" } ] }, { "id": "8afc807c-5310-4124-bd43-e90b589a304f", "type": "variant", "text": [ "(H558R) " ], "offsets": [ [ 1254, 1262 ] ], "normalized": [ { "db_name": "dbSNP", "db_id": "1805124" } ] }, { "id": "6bbb2b65-c90e-4bee-805a-873a93e913cf", "type": "variant", "text": [ "C5457T " ], "offsets": [ [ 1295, 1302 ] ], "normalized": [ { "db_name": "dbSNP", "db_id": "1805126" } ] }, { "id": "c263ca0e-e785-450e-9d4c-9415cc2bb64f", "type": "variant", "text": [ "(D1819D) " ], "offsets": [ [ 1305, 1314 ] ], "normalized": [ { "db_name": "dbSNP", "db_id": "1805126" } ] }, { "id": "530956e5-5779-4972-95d2-8799a5c3e572", "type": "variant", "text": [ "G1673" ], "offsets": [ [ 1775, 1780 ] ], "normalized": [ { "db_name": "dbSNP", "db_id": "1805124" } ] }, { "id": "f622b6b7-afac-4713-a46e-71e506b71189", "type": "variant", "text": [ "(R558)" ], "offsets": [ [ 1783, 1789 ] ], "normalized": [ { "db_name": "dbSNP", "db_id": "1805124" } ] }, { "id": "8e5590f1-2c51-46f2-9c6d-daba0cfe7197", "type": "variant", "text": [ "A1673G" ], "offsets": [ [ 1244, 1250 ] ], "normalized": [ { "db_name": "dbSNP", "db_id": "1805124" } ] } ]	[]	[]	[]
103	15164150	[ { "id": "435ae0f2-2ee0-425a-bdff-6a0628ed381f", "type": "title", "text": [ "Evaluation of the role of the SQSTM1 gene in sporadic Belgian patients with Paget's disease." ], "offsets": [ [ 0, 94 ] ] }, { "id": "97af01e4-3ede-4eb7-9e93-0bfcf300cdfc", "type": "abstract", "text": [ "A positional cloning effort in French Canadian families with Paget's disease of bone (PDB) resulted in the identification of a mutation in the sequestosome1 ( SQSTM1 ) gene in a subset of both familial and sporadic PDB cases. This was confirmed in samples of mainly United Kingdom (UK) origin. In this study, we performed both mutation analysis and association studies in order to evaluate the role of this gene in a collection of isolated Belgian PDB patients. A mutation in the SQSTM1 gene was found in only 6 of 111 patients (5.4%). In all cases it involves the P392L mutation, previously shown to be common in both familial and sporadic cases. To perform association studies, we selected 8 single nucleotide polymorphisms (SNPs) and looked for linkage disequilibrium (LD) between these. Haplotype analysis indicated that typing of 3 Tag SNPs ( IVS1 + 633A/C , IVS5 - 23A/G , and 976A/G ) enables us to identify the most common haplotypes. Association studies for the 3 selected SNPs, based on 105 PDB cases without a SQSTM1 mutation and 159 control individuals, did not support a possible influence of natural variants in the SQSTM1 gene either on the pathogenesis of PDB or on the disease severity. In conclusion, our study confirms that the P392L mutation is a recurrent mutation causing PDB in different populations. We were not able to show an association between SQSTM1 polymorphisms and PDB in our population but this clearly needs to be extended to other populations. The presented identification of haplotype Tag SNPs will be of major help for such studies." ], "offsets": [ [ 95, 1680 ] ] } ]	[ { "id": "be24ee60-59cc-4e23-973a-779e4ffd6b97", "type": "gene", "text": [ "sequestosome1" ], "offsets": [ [ 239, 252 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "8878" } ] }, { "id": "c4a72754-14a3-4387-b684-3fb3fa4a9b41", "type": "gene", "text": [ "SQSTM1" ], "offsets": [ [ 31, 37 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "8878" } ] }, { "id": "1f3c78d6-b352-4975-abb0-b3a15ea89159", "type": "gene", "text": [ "SQSTM1" ], "offsets": [ [ 31, 37 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "8878" } ] }, { "id": "c1aa00ff-4006-4936-8095-7265adb56b4e", "type": "gene", "text": [ "SQSTM1" ], "offsets": [ [ 31, 37 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "8878" } ] }, { "id": "1dfe384d-facf-4846-8f63-9e875d129a00", "type": "gene", "text": [ "SQSTM1" ], "offsets": [ [ 31, 37 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "8878" } ] }, { "id": "7b410e08-69e2-4ea4-8ad0-81ac8f491117", "type": "gene", "text": [ "SQSTM1" ], "offsets": [ [ 31, 37 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "8878" } ] }, { "id": "0e93873c-1ef8-4116-823c-44f86f6936df", "type": "variant", "text": [ "P392L" ], "offsets": [ [ 665, 670 ] ], "normalized": [ { "db_name": "HGVS-like", "db_id": "P392L" } ] }, { "id": "e18f1f03-c1e3-4f6d-bb2d-3d961ff112af", "type": "variant", "text": [ "IVS1 + 633A/C" ], "offsets": [ [ 949, 962 ] ], "normalized": [ { "db_name": "HGVS-like", "db_id": "A633C" } ] }, { "id": "69f44b40-6ca1-4432-8a4d-53a4aaf9c9bf", "type": "variant", "text": [ "IVS5 - 23A/G" ], "offsets": [ [ 966, 978 ] ], "normalized": [ { "db_name": "dbSNP", "db_id": "2241349" } ] }, { "id": "450dd760-ab5d-4dd6-bc19-11d8775e4e2f", "type": "variant", "text": [ "976A/G" ], "offsets": [ [ 986, 992 ] ], "normalized": [ { "db_name": "HGVS-like", "db_id": "A976G" } ] }, { "id": "71c51e07-d0e7-43c1-8dff-153144acca55", "type": "variant", "text": [ "P392L" ], "offsets": [ [ 665, 670 ] ], "normalized": [ { "db_name": "HGVS-like", "db_id": "P392L" } ] } ]	[]	[]	[]
104	15166293	[ { "id": "c931e56e-ec7a-4e70-9902-5363983d985d", "type": "title", "text": [ "Melanin-concentrating hormone receptor mutations and human obesity: functional analysis." ], "offsets": [ [ 0, 88 ] ] }, { "id": "be6da078-cae5-450f-ba71-8f3af30545ea", "type": "abstract", "text": [ "Melanin-concentrating hormone (MCH) , a neuropeptide highly expressed in the lateral hypothalamus, has an important role in the regulation of energy balance and body weight in rodents. We examined whether mutations in the two known MCH receptors might be associated with obesity-related phenotypes in humans. Among 106 subjects with severe early onset obesity and a history of hyperphagia, we found two missense variants in MCHR1 : Y181H and R248Q . Neither of these was found in 192 normal weight controls. R248Q cosegregated with obesity across two generations; family data were unavailable for Y181H . When expressed in HEK293 cells, R248Q showed no evidence of constitutive activation or ligand hypersensitivity for extracellular signal-regulated kinase phosphorylation. In addition, R248Q showed no enhanced suppression of cAMP generation. Two common single-nucleotide polymorphisms were found to be in linkage disequilibrium: g.-114A>G and c.39C>T . No association between either of these single-nucleotide polymorphisms and obesity-related phenotypes was found among a population cohort of 541 whites. Only two rare noncoding variants were found in MCHR2 . In conclusion, mutations in the MCH receptors are not commonly found in humans with severe early onset obesity. Clarification of the relationship of these variants to obesity must await study in other populations and/or in genetically modified mice." ], "offsets": [ [ 89, 1517 ] ] } ]	[ { "id": "65b2fb84-cd79-41ca-9b9a-74335420c603", "type": "gene", "text": [ "Melanin-concentrating hormone (MCH)" ], "offsets": [ [ 89, 124 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "5367" } ] }, { "id": "009fa383-c630-436f-97b4-ad5d95d2c8f1", "type": "gene", "text": [ "MCHR1" ], "offsets": [ [ 514, 519 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "2847" } ] }, { "id": "1b8c0d4e-0dd0-47b4-99f6-fff474a91adf", "type": "gene", "text": [ "MCHR2" ], "offsets": [ [ 1260, 1265 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "84539" } ] }, { "id": "85a54f47-cffd-4ed6-9c83-f58f7c1a1828", "type": "variant", "text": [ "Y181H" ], "offsets": [ [ 523, 528 ] ], "normalized": [ { "db_name": "HGVS-like", "db_id": "Y181H" } ] }, { "id": "6c6f2148-b2b2-4288-84d6-cfa52fab1c57", "type": "variant", "text": [ "R248Q" ], "offsets": [ [ 535, 540 ] ], "normalized": [ { "db_name": "HGVS-like", "db_id": "R248Q" } ] }, { "id": "31f736e3-796b-475b-8acd-3ee17308258c", "type": "variant", "text": [ "R248Q" ], "offsets": [ [ 535, 540 ] ], "normalized": [ { "db_name": "HGVS-like", "db_id": "R248Q" } ] }, { "id": "04069184-3b26-4c72-a780-7f97d3af82d4", "type": "variant", "text": [ "Y181H" ], "offsets": [ [ 523, 528 ] ], "normalized": [ { "db_name": "HGVS-like", "db_id": "Y181H" } ] }, { "id": "15972e81-022a-423e-90ac-895ab255c23b", "type": "variant", "text": [ "R248Q" ], "offsets": [ [ 535, 540 ] ], "normalized": [ { "db_name": "HGVS-like", "db_id": "R248Q" } ] }, { "id": "72398634-26b0-4e34-b198-27665f4bbcbe", "type": "variant", "text": [ "R248Q" ], "offsets": [ [ 535, 540 ] ], "normalized": [ { "db_name": "HGVS-like", "db_id": "R248Q" } ] }, { "id": "1fc54a89-f17f-4003-b168-c2548c0b2bef", "type": "variant", "text": [ "g.-114A>G" ], "offsets": [ [ 1033, 1042 ] ], "normalized": [ { "db_name": "HGVS-like", "db_id": "A-114G" } ] }, { "id": "00d11eef-1dfa-4d70-b312-7bfe95bd9a58", "type": "variant", "text": [ "c.39C>T" ], "offsets": [ [ 1049, 1056 ] ], "normalized": [ { "db_name": "HGVS-like", "db_id": "C39T" } ] } ]	[]	[]	[]
105	15170937	[ { "id": "7d4b847d-a907-44cf-8d37-636dcbc69fc0", "type": "title", "text": [ "Association of single nucleotide polymorphisms within cytokine genes with juvenile idiopathic arthritis in the Czech population." ], "offsets": [ [ 0, 128 ] ] }, { "id": "e214b9ae-ce9a-4d10-9147-1c6aa177fc75", "type": "abstract", "text": [ "OBJECTIVE: To examine the possible association of juvenile idiopathic arthritis (JIA) with polymorphisms within cytokine genes in the Czech population. METHODS: In a case-control study, genotypes of 130 patients with JIA (63 male, 67 female; age at onset 7.6 +/- 4.4 yrs; 43 oligoarticular, 72 polyarticular, 15 systemic form) were compared to 102 healthy unrelated blood donors. Using the polymerase chain reaction technique with sequence-specific primers from the 13th IHWG workshop, we analyzed 19 single nucleotide polymorphisms within 12 different cytokine genes [ interleukin (IL)-1a , IL-1beta , IL-2 , IL-4 , IL-6 , IL-10 , IL-12 , transforming growth factor (TGF)-beta , interferon (IFN)-g ], and related molecules ( IL-1R , IL-1RA , IL-4Ra ). Genotype frequencies were compared using chi-square analysis, and the significance level was corrected for the number of independent tests. RESULTS: Significant positive association was found for the G allele of the IL-4 -1098 T/G polymorphism, which was carried by 10% of cases and 25% of controls [odds ratio (OR) 0.32, 95% confidence interval (CI) 0.16-0.67, corrected p = 0.038). Also, a nonsignificant increase in the frequency of the IL-1beta +3962 C allele was detected in cases (96%) versus controls (84%) (OR 4.65, 95% CI 1.64-13.2, corrected p = 0.091). We did not replicate previously found associations with the IL-1a , IL-6 , IL-10 , and IL-1R IL-1RA polymorphisms. CONCLUSION: Our study showed association with JIA for the IL-4 -1098 T/G polymorphism. It also underlines the genetic contribution of IL-1 polymorphisms to the pathogenesis of JIA, as another polymorphism within the IL-1beta may influence the risk of the disease." ], "offsets": [ [ 129, 1853 ] ] } ]	[ { "id": "af923b8e-fe26-4473-8803-3c08d41c1c7d", "type": "gene", "text": [ "interleukin (IL)-1a" ], "offsets": [ [ 699, 718 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "3552" } ] }, { "id": "2ed19056-ee6a-467b-88eb-c6754ba7e59c", "type": "gene", "text": [ "IL-1beta" ], "offsets": [ [ 722, 730 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "3553" } ] }, { "id": "686b4ae0-4cac-4abc-b07c-2f87905d9381", "type": "gene", "text": [ "IL-2" ], "offsets": [ [ 734, 738 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "3558" } ] }, { "id": "e2ac5dad-3f41-466f-a8be-f7c3c05c19a9", "type": "gene", "text": [ "IL-4" ], "offsets": [ [ 742, 746 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "3565" } ] }, { "id": "177bb61c-9d1e-442b-befb-c691dcaa4b96", "type": "gene", "text": [ "IL-6" ], "offsets": [ [ 750, 754 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "3569" } ] }, { "id": "a0d77636-4559-4ef1-a0b8-59ce0a0fbd20", "type": "gene", "text": [ "IL-10" ], "offsets": [ [ 758, 763 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "3586" } ] }, { "id": "efb5452b-a66c-4271-ab61-fb6102f7e525", "type": "gene", "text": [ "IL-12" ], "offsets": [ [ 767, 772 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "No" } ] }, { "id": "0c0948fd-dcb0-452c-a654-a95964659643", "type": "gene", "text": [ "transforming growth factor (TGF)-beta" ], "offsets": [ [ 776, 813 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "7040" } ] }, { "id": "958c8624-65fe-41e2-83d5-24b2b5a29a23", "type": "gene", "text": [ "interferon (IFN)-g" ], "offsets": [ [ 817, 835 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "No" } ] }, { "id": "a97c5505-1a78-4269-bb98-d4c91002f90c", "type": "gene", "text": [ "IL-1R" ], "offsets": [ [ 863, 868 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "3554" } ] }, { "id": "0895fa45-069e-4882-87b9-2f8a7ad50a11", "type": "gene", "text": [ "IL-1RA" ], "offsets": [ [ 872, 878 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "3557" } ] }, { "id": "05633bc9-9af6-4f74-8708-1b300551db7a", "type": "gene", "text": [ "IL-4Ra" ], "offsets": [ [ 882, 888 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "3566" } ] }, { "id": "947ad686-7d21-490f-a007-ed6b7f91897e", "type": "gene", "text": [ "IL-4" ], "offsets": [ [ 742, 746 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "3565" } ] }, { "id": "e4f3f499-8d71-44e3-aafd-7b9901f4ce77", "type": "gene", "text": [ "IL-1beta" ], "offsets": [ [ 722, 730 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "3553" } ] }, { "id": "5528af4e-785e-47f6-88ff-ba2e50403008", "type": "gene", "text": [ "IL-1a" ], "offsets": [ [ 1525, 1530 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "3552" } ] }, { "id": "5b18a7b8-a92b-4928-bcc2-17c3f2991f53", "type": "gene", "text": [ "IL-6" ], "offsets": [ [ 750, 754 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "3569" } ] }, { "id": "1484bc39-e082-4deb-a038-da9b82fba015", "type": "gene", "text": [ "IL-10" ], "offsets": [ [ 758, 763 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "3586" } ] }, { "id": "d61e3370-c68d-4ba6-b451-66913ac392ce", "type": "gene", "text": [ "IL-1R" ], "offsets": [ [ 863, 868 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "3554" } ] }, { "id": "0cd47e80-800b-4f92-9aca-a5759045c592", "type": "gene", "text": [ "IL-1RA" ], "offsets": [ [ 872, 878 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "3557" } ] }, { "id": "a946b974-04ef-4b20-b2f5-d51b0a0fcbef", "type": "gene", "text": [ "IL-4" ], "offsets": [ [ 742, 746 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "3565" } ] }, { "id": "864e3a8d-612a-4fda-9673-cdb7abae77f5", "type": "gene", "text": [ "IL-1beta" ], "offsets": [ [ 722, 730 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "3553" } ] }, { "id": "2866649e-60d1-4347-9995-4132a040a998", "type": "variant", "text": [ "-1098 T/G" ], "offsets": [ [ 1116, 1125 ] ], "normalized": [ { "db_name": "HGVS-like", "db_id": "T-1098G" } ] }, { "id": "59db1f4d-6219-4617-a9cf-a068c8d5039c", "type": "variant", "text": [ "+3962 C" ], "offsets": [ [ 1348, 1355 ] ], "normalized": [ { "db_name": "HGVS-like", "db_id": "3962C" } ] }, { "id": "9c1fcdd6-4cb6-41c9-bb48-4ed9b84d2991", "type": "variant", "text": [ "-1098 T/G" ], "offsets": [ [ 1116, 1125 ] ], "normalized": [ { "db_name": "HGVS-like", "db_id": "T-1098G" } ] } ]	[]	[]	[]

101

15150650

[ { "id": "fc75aa4a-caba-4f68-a13a-325f9117cdec", "type": "title", "text": [ "The allelic variant of LAR gene promoter -127 bp T-->A is associated with reduced risk of obesity and other features related to insulin resistance." ], "offsets": [ [ 0, 153 ] ] }, { "id": "c5abebc1-28c4-4b1b-b1b8-6addad3944d4", "type": "abstract", "text": [ "Insulin resistance, which is pathogenic for type 2 diabetes (T2D), is under the control of largely unknown genetic determinants. LAR , a protein-tyrosine phosphatase which inhibits insulin signalling, is overexpressed in animal and human models of insulin resistance. We studied the entire sequence of the LAR gene by SSCP analysis and automatic DNA sequencing, with the aim of verifying whether its sequence variants might be associated with insulin resistance. In the 276 bp sequence upstream of the transcriptional start site (i.e. a region we have identified as having basal promoter activity) a -127 bp T-->A SNP (5% frequency) was associated with lower body mass index (BMI) ( P=0.03), waist circumference ( P=0.01), blood pressure ( P=0.01) and urinary albumin/creatinine ratio ( P=0.04) in 589 non-diabetic unrelated individuals from the Gargano region (central east coast of Italy). To quantify the risk for a high body weight conferred by the -127 T-->A SNP, the whole cohort was divided into tertiles according to the individual BMI. The risk of belonging to the heavier tertile, as compared to the leaner one, was reduced by approximately 60%. In a population from East Sicily ( n=307), T/A genotype carriers ( n=13) showed lower triglyceride levels ( P=0.04) and higher insulin sensitivity as indicated by lower plasma glucose ( P=0.03) and serum insulin ( P=0.006) during oral glucose tolerance testing (OGTT). Promoter activity, studied by cDNA transfection experiments, was similar for the A and T alleles. In conclusion, a genetic variant of the LAR gene promoter is consistently associated with features of insulin resistance in two different Caucasian populations. Although the biological relevance of this variant has yet to be determined, this finding underlines the potential importance of the LAR gene in dysregulation of insulin sensitivity and related disorders." ], "offsets": [ [ 154, 2067 ] ] } ]

[ { "id": "3153d8a4-4361-4ffc-8fb0-89553ee6119a", "type": "gene", "text": [ "Insulin" ], "offsets": [ [ 154, 161 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "3630" } ] }, { "id": "c21f43a0-db80-4cb9-9b76-b13cf6a290e8", "type": "gene", "text": [ "LAR" ], "offsets": [ [ 24, 27 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "5792" } ] }, { "id": "06772945-bf4e-4382-95ef-3835c4faafa5", "type": "gene", "text": [ "insulin" ], "offsets": [ [ 133, 140 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "3630" } ] }, { "id": "817f2145-ebaa-4051-b769-4e5763e5a563", "type": "gene", "text": [ "insulin" ], "offsets": [ [ 133, 140 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "3630" } ] }, { "id": "a445999b-017b-4403-a48c-a6e1bc1287f0", "type": "gene", "text": [ "LAR" ], "offsets": [ [ 24, 27 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "5792" } ] }, { "id": "83786043-e198-4d07-bf11-05d876c79185", "type": "gene", "text": [ "insulin" ], "offsets": [ [ 133, 140 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "3630" } ] }, { "id": "6e109683-485c-414d-8683-685b5d3196b6", "type": "gene", "text": [ "insulin" ], "offsets": [ [ 133, 140 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "3630" } ] }, { "id": "d6e04615-5e4c-4d68-8682-525c4c288c34", "type": "gene", "text": [ "insulin" ], "offsets": [ [ 133, 140 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "3630" } ] }, { "id": "d1d8c084-ec05-4eaf-bc85-63b47ef3fabe", "type": "gene", "text": [ "LAR" ], "offsets": [ [ 24, 27 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "5792" } ] }, { "id": "c7ee4786-b5d7-40cf-876b-0ac27a0a3d43", "type": "gene", "text": [ "insulin" ], "offsets": [ [ 133, 140 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "3630" } ] }, { "id": "5521f810-6072-471d-885c-cbf08899d24e", "type": "gene", "text": [ "LAR" ], "offsets": [ [ 24, 27 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "5792" } ] }, { "id": "351e5e8b-b5be-480b-9870-46f5a66e0870", "type": "gene", "text": [ "insulin" ], "offsets": [ [ 133, 140 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "3630" } ] }, { "id": "df734e6e-b723-476a-a3d1-1896d92d4b44", "type": "variant", "text": [ "-127 bp T-->A" ], "offsets": [ [ 44, 57 ] ], "normalized": [ { "db_name": "dbSNP", "db_id": "3001722" } ] }, { "id": "81a361d8-a925-4487-9a96-0b2715006d79", "type": "variant", "text": [ "-127 T-->A" ], "offsets": [ [ 1120, 1130 ] ], "normalized": [ { "db_name": "dbSNP", "db_id": "3001722" } ] } ]

[]

102

15161528

[ { "id": "1f68e7de-096b-4068-b87a-df10c157d752", "type": "title", "text": [ "Single nucleotide polymorphisms of the SCN5A gene in Han Chinese and their relation with Brugada syndrome." ], "offsets": [ [ 0, 108 ] ] }, { "id": "68872a56-83a9-4162-be79-dc0b42e466c7", "type": "abstract", "text": [ "BACKGROUND: Mutations in the cardiac sodium channel gene ( SCN5A ) may lead to a broad spectrum of familial arrhythmias, including long QT syndrome (LQTS), idiopathic ventricular fibrillation (IVF), and isolated cardiac conduction diseases. Recent studies have shown that polymorphisms in the SCN5A gene also play an important role in the manifestation of disorders involving cardiac excitability. In this study, we investigated the polymorphisms of the SCN5A gene in Han Chinese and its relation to Brugada syndrome (BS). METHODS: Genomic DNA was isolated from 120 unrelated healthy volunteers and 48 unrelated Brugada syndrome patients by means of standard procedures. All exons including the putative splicing sites of the SCN5A gene were amplified by PCR and sequenced directly or after subcloning using an ABI Prism 377 DNA sequencer. RESULTS: A total of 5 single nucleotide polymorphisms (SNPs) were identified in the Han Chinese population, including 3 novel ones: G87A (A29A) , 4245 + 82A > G , and G6174A . The allele frequencies of each SNP in the Han Chinese population were as follows: G87A (A29A) 27.5%, A1673G (H558R) 10.4%, 4245 + 82A > G 32.8%, C5457T (D1819D) 41.3%, and G6174A 44.9%. S1102Y and 10 other SNPs identified in other ethnic populations were not detected in this study. There was no significant difference in the allele frequency of A1673G (H558R) between different ethnic populations (all P > 0.5). On the other hand, the allele frequency of C5457T (D1819D) among Han Chinese was similar to its frequency among Japanese (P > 0.5), but higher than that among Americans (P < 0.005). The allele G1673 (R558) was over-represented in BS patients compared to controls (P < 0.005), but there was no significant difference in genotype frequencies at this locus. There were also no differences in either the allele or genotype frequencies of the 4 other identified SNPs when comparing BS patients with healthy controls. CONCLUSIONS: The distribution of SCN5A SNPs may vary between different ethnicities. The polymorphism of A1673G might be associated with BS and may contribute to a susceptibility to BS in Han Chinese." ], "offsets": [ [ 109, 2300 ] ] } ]

[ { "id": "942203bc-1533-49fc-9227-199c383e2162", "type": "gene", "text": [ "cardiac sodium channel gene" ], "offsets": [ [ 139, 166 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "6331" } ] }, { "id": "cad0b594-47c7-4765-9722-93800e3d1fb4", "type": "gene", "text": [ "SCN5A" ], "offsets": [ [ 40, 45 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "6331" } ] }, { "id": "4b138e56-7ad7-468c-84d8-7c95c70661de", "type": "gene", "text": [ "SCN5A" ], "offsets": [ [ 40, 45 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "6331" } ] }, { "id": "bcb70aa8-df10-4972-a478-c5e4465443df", "type": "gene", "text": [ "SCN5A" ], "offsets": [ [ 40, 45 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "6331" } ] }, { "id": "6493f585-b971-46e5-a39a-44a28e912a59", "type": "gene", "text": [ "SCN5A" ], "offsets": [ [ 40, 45 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "6331" } ] }, { "id": "bd0a5f45-6401-4eb4-b129-ce20bb3ae385", "type": "gene", "text": [ "SCN5A" ], "offsets": [ [ 40, 45 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "6331" } ] }, { "id": "f8a4ad84-d64b-4dc4-a99c-c10d98bba00e", "type": "variant", "text": [ "G87A" ], "offsets": [ [ 1090, 1094 ] ], "normalized": [ { "db_name": "dbSNP", "db_id": "6599230" } ] }, { "id": "9b732b5c-2359-4b54-892d-1b17a5880130", "type": "variant", "text": [ "(A29A)" ], "offsets": [ [ 1097, 1103 ] ], "normalized": [ { "db_name": "dbSNP", "db_id": "6599230" } ] }, { "id": "c8e19412-6709-414d-bf3a-8bfefb72c94d", "type": "variant", "text": [ "4245 + 82A > G" ], "offsets": [ [ 1107, 1121 ] ], "normalized": [ { "db_name": "HGVS-like", "db_id": "A82G" } ] }, { "id": "61b4edf1-d937-4348-8135-85168cda498d", "type": "variant", "text": [ "G6174A" ], "offsets": [ [ 1129, 1135 ] ], "normalized": [ { "db_name": "HGVS-like", "db_id": "G6174A" } ] }, { "id": "e3a0c63c-8f6c-4d7a-8025-101db6989e41", "type": "variant", "text": [ "G87A" ], "offsets": [ [ 1090, 1094 ] ], "normalized": [ { "db_name": "dbSNP", "db_id": "6599230" } ] }, { "id": "2195feb1-9762-413f-9aa9-b0450b2eec69", "type": "variant", "text": [ "(A29A)" ], "offsets": [ [ 1097, 1103 ] ], "normalized": [ { "db_name": "dbSNP", "db_id": "6599230" } ] }, { "id": "186c6d2a-9b7b-4f5c-ac56-84360f79e6f9", "type": "variant", "text": [ "A1673G " ], "offsets": [ [ 1244, 1251 ] ], "normalized": [ { "db_name": "dbSNP", "db_id": "1805124" } ] }, { "id": "a8695a12-c7ee-431b-83eb-ee9865bec933", "type": "variant", "text": [ "(H558R) " ], "offsets": [ [ 1254, 1262 ] ], "normalized": [ { "db_name": "dbSNP", "db_id": "1805124" } ] }, { "id": "5f397eb0-e2df-450e-9325-0484d7696045", "type": "variant", "text": [ "4245 + 82A > G" ], "offsets": [ [ 1107, 1121 ] ], "normalized": [ { "db_name": "HGVS-like", "db_id": "A82G" } ] }, { "id": "9ca82397-b598-4667-93b2-cd6ebc00e21c", "type": "variant", "text": [ "C5457T " ], "offsets": [ [ 1295, 1302 ] ], "normalized": [ { "db_name": "dbSNP", "db_id": "1805126" } ] }, { "id": "0c925751-a6ab-498f-b206-cd8046ece86c", "type": "variant", "text": [ "(D1819D) " ], "offsets": [ [ 1305, 1314 ] ], "normalized": [ { "db_name": "dbSNP", "db_id": "1805126" } ] }, { "id": "a6f89dc3-d7c9-4ff4-b824-2e479ca256a5", "type": "variant", "text": [ "G6174A" ], "offsets": [ [ 1129, 1135 ] ], "normalized": [ { "db_name": "HGVS-like", "db_id": "G6174A" } ] }, { "id": "8e44bc70-72d9-4e60-a5c0-350301d1639d", "type": "variant", "text": [ "S1102Y" ], "offsets": [ [ 1343, 1349 ] ], "normalized": [ { "db_name": "dbSNP", "db_id": "7626962" } ] }, { "id": "a706a7e5-7873-424d-b6fa-8325910ba173", "type": "variant", "text": [ "A1673G " ], "offsets": [ [ 1244, 1251 ] ], "normalized": [ { "db_name": "dbSNP", "db_id": "1805124" } ] }, { "id": "8afc807c-5310-4124-bd43-e90b589a304f", "type": "variant", "text": [ "(H558R) " ], "offsets": [ [ 1254, 1262 ] ], "normalized": [ { "db_name": "dbSNP", "db_id": "1805124" } ] }, { "id": "6bbb2b65-c90e-4bee-805a-873a93e913cf", "type": "variant", "text": [ "C5457T " ], "offsets": [ [ 1295, 1302 ] ], "normalized": [ { "db_name": "dbSNP", "db_id": "1805126" } ] }, { "id": "c263ca0e-e785-450e-9d4c-9415cc2bb64f", "type": "variant", "text": [ "(D1819D) " ], "offsets": [ [ 1305, 1314 ] ], "normalized": [ { "db_name": "dbSNP", "db_id": "1805126" } ] }, { "id": "530956e5-5779-4972-95d2-8799a5c3e572", "type": "variant", "text": [ "G1673" ], "offsets": [ [ 1775, 1780 ] ], "normalized": [ { "db_name": "dbSNP", "db_id": "1805124" } ] }, { "id": "f622b6b7-afac-4713-a46e-71e506b71189", "type": "variant", "text": [ "(R558)" ], "offsets": [ [ 1783, 1789 ] ], "normalized": [ { "db_name": "dbSNP", "db_id": "1805124" } ] }, { "id": "8e5590f1-2c51-46f2-9c6d-daba0cfe7197", "type": "variant", "text": [ "A1673G" ], "offsets": [ [ 1244, 1250 ] ], "normalized": [ { "db_name": "dbSNP", "db_id": "1805124" } ] } ]

[]

103

15164150

[ { "id": "435ae0f2-2ee0-425a-bdff-6a0628ed381f", "type": "title", "text": [ "Evaluation of the role of the SQSTM1 gene in sporadic Belgian patients with Paget's disease." ], "offsets": [ [ 0, 94 ] ] }, { "id": "97af01e4-3ede-4eb7-9e93-0bfcf300cdfc", "type": "abstract", "text": [ "A positional cloning effort in French Canadian families with Paget's disease of bone (PDB) resulted in the identification of a mutation in the sequestosome1 ( SQSTM1 ) gene in a subset of both familial and sporadic PDB cases. This was confirmed in samples of mainly United Kingdom (UK) origin. In this study, we performed both mutation analysis and association studies in order to evaluate the role of this gene in a collection of isolated Belgian PDB patients. A mutation in the SQSTM1 gene was found in only 6 of 111 patients (5.4%). In all cases it involves the P392L mutation, previously shown to be common in both familial and sporadic cases. To perform association studies, we selected 8 single nucleotide polymorphisms (SNPs) and looked for linkage disequilibrium (LD) between these. Haplotype analysis indicated that typing of 3 Tag SNPs ( IVS1 + 633A/C , IVS5 - 23A/G , and 976A/G ) enables us to identify the most common haplotypes. Association studies for the 3 selected SNPs, based on 105 PDB cases without a SQSTM1 mutation and 159 control individuals, did not support a possible influence of natural variants in the SQSTM1 gene either on the pathogenesis of PDB or on the disease severity. In conclusion, our study confirms that the P392L mutation is a recurrent mutation causing PDB in different populations. We were not able to show an association between SQSTM1 polymorphisms and PDB in our population but this clearly needs to be extended to other populations. The presented identification of haplotype Tag SNPs will be of major help for such studies." ], "offsets": [ [ 95, 1680 ] ] } ]

[ { "id": "be24ee60-59cc-4e23-973a-779e4ffd6b97", "type": "gene", "text": [ "sequestosome1" ], "offsets": [ [ 239, 252 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "8878" } ] }, { "id": "c4a72754-14a3-4387-b684-3fb3fa4a9b41", "type": "gene", "text": [ "SQSTM1" ], "offsets": [ [ 31, 37 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "8878" } ] }, { "id": "1f3c78d6-b352-4975-abb0-b3a15ea89159", "type": "gene", "text": [ "SQSTM1" ], "offsets": [ [ 31, 37 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "8878" } ] }, { "id": "c1aa00ff-4006-4936-8095-7265adb56b4e", "type": "gene", "text": [ "SQSTM1" ], "offsets": [ [ 31, 37 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "8878" } ] }, { "id": "1dfe384d-facf-4846-8f63-9e875d129a00", "type": "gene", "text": [ "SQSTM1" ], "offsets": [ [ 31, 37 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "8878" } ] }, { "id": "7b410e08-69e2-4ea4-8ad0-81ac8f491117", "type": "gene", "text": [ "SQSTM1" ], "offsets": [ [ 31, 37 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "8878" } ] }, { "id": "0e93873c-1ef8-4116-823c-44f86f6936df", "type": "variant", "text": [ "P392L" ], "offsets": [ [ 665, 670 ] ], "normalized": [ { "db_name": "HGVS-like", "db_id": "P392L" } ] }, { "id": "e18f1f03-c1e3-4f6d-bb2d-3d961ff112af", "type": "variant", "text": [ "IVS1 + 633A/C" ], "offsets": [ [ 949, 962 ] ], "normalized": [ { "db_name": "HGVS-like", "db_id": "A633C" } ] }, { "id": "69f44b40-6ca1-4432-8a4d-53a4aaf9c9bf", "type": "variant", "text": [ "IVS5 - 23A/G" ], "offsets": [ [ 966, 978 ] ], "normalized": [ { "db_name": "dbSNP", "db_id": "2241349" } ] }, { "id": "450dd760-ab5d-4dd6-bc19-11d8775e4e2f", "type": "variant", "text": [ "976A/G" ], "offsets": [ [ 986, 992 ] ], "normalized": [ { "db_name": "HGVS-like", "db_id": "A976G" } ] }, { "id": "71c51e07-d0e7-43c1-8dff-153144acca55", "type": "variant", "text": [ "P392L" ], "offsets": [ [ 665, 670 ] ], "normalized": [ { "db_name": "HGVS-like", "db_id": "P392L" } ] } ]

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104

15166293

[ { "id": "c931e56e-ec7a-4e70-9902-5363983d985d", "type": "title", "text": [ "Melanin-concentrating hormone receptor mutations and human obesity: functional analysis." ], "offsets": [ [ 0, 88 ] ] }, { "id": "be6da078-cae5-450f-ba71-8f3af30545ea", "type": "abstract", "text": [ "Melanin-concentrating hormone (MCH) , a neuropeptide highly expressed in the lateral hypothalamus, has an important role in the regulation of energy balance and body weight in rodents. We examined whether mutations in the two known MCH receptors might be associated with obesity-related phenotypes in humans. Among 106 subjects with severe early onset obesity and a history of hyperphagia, we found two missense variants in MCHR1 : Y181H and R248Q . Neither of these was found in 192 normal weight controls. R248Q cosegregated with obesity across two generations; family data were unavailable for Y181H . When expressed in HEK293 cells, R248Q showed no evidence of constitutive activation or ligand hypersensitivity for extracellular signal-regulated kinase phosphorylation. In addition, R248Q showed no enhanced suppression of cAMP generation. Two common single-nucleotide polymorphisms were found to be in linkage disequilibrium: g.-114A>G and c.39C>T . No association between either of these single-nucleotide polymorphisms and obesity-related phenotypes was found among a population cohort of 541 whites. Only two rare noncoding variants were found in MCHR2 . In conclusion, mutations in the MCH receptors are not commonly found in humans with severe early onset obesity. Clarification of the relationship of these variants to obesity must await study in other populations and/or in genetically modified mice." ], "offsets": [ [ 89, 1517 ] ] } ]

[ { "id": "65b2fb84-cd79-41ca-9b9a-74335420c603", "type": "gene", "text": [ "Melanin-concentrating hormone (MCH)" ], "offsets": [ [ 89, 124 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "5367" } ] }, { "id": "009fa383-c630-436f-97b4-ad5d95d2c8f1", "type": "gene", "text": [ "MCHR1" ], "offsets": [ [ 514, 519 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "2847" } ] }, { "id": "1b8c0d4e-0dd0-47b4-99f6-fff474a91adf", "type": "gene", "text": [ "MCHR2" ], "offsets": [ [ 1260, 1265 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "84539" } ] }, { "id": "85a54f47-cffd-4ed6-9c83-f58f7c1a1828", "type": "variant", "text": [ "Y181H" ], "offsets": [ [ 523, 528 ] ], "normalized": [ { "db_name": "HGVS-like", "db_id": "Y181H" } ] }, { "id": "6c6f2148-b2b2-4288-84d6-cfa52fab1c57", "type": "variant", "text": [ "R248Q" ], "offsets": [ [ 535, 540 ] ], "normalized": [ { "db_name": "HGVS-like", "db_id": "R248Q" } ] }, { "id": "31f736e3-796b-475b-8acd-3ee17308258c", "type": "variant", "text": [ "R248Q" ], "offsets": [ [ 535, 540 ] ], "normalized": [ { "db_name": "HGVS-like", "db_id": "R248Q" } ] }, { "id": "04069184-3b26-4c72-a780-7f97d3af82d4", "type": "variant", "text": [ "Y181H" ], "offsets": [ [ 523, 528 ] ], "normalized": [ { "db_name": "HGVS-like", "db_id": "Y181H" } ] }, { "id": "15972e81-022a-423e-90ac-895ab255c23b", "type": "variant", "text": [ "R248Q" ], "offsets": [ [ 535, 540 ] ], "normalized": [ { "db_name": "HGVS-like", "db_id": "R248Q" } ] }, { "id": "72398634-26b0-4e34-b198-27665f4bbcbe", "type": "variant", "text": [ "R248Q" ], "offsets": [ [ 535, 540 ] ], "normalized": [ { "db_name": "HGVS-like", "db_id": "R248Q" } ] }, { "id": "1fc54a89-f17f-4003-b168-c2548c0b2bef", "type": "variant", "text": [ "g.-114A>G" ], "offsets": [ [ 1033, 1042 ] ], "normalized": [ { "db_name": "HGVS-like", "db_id": "A-114G" } ] }, { "id": "00d11eef-1dfa-4d70-b312-7bfe95bd9a58", "type": "variant", "text": [ "c.39C>T" ], "offsets": [ [ 1049, 1056 ] ], "normalized": [ { "db_name": "HGVS-like", "db_id": "C39T" } ] } ]

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105

15170937

[ { "id": "7d4b847d-a907-44cf-8d37-636dcbc69fc0", "type": "title", "text": [ "Association of single nucleotide polymorphisms within cytokine genes with juvenile idiopathic arthritis in the Czech population." ], "offsets": [ [ 0, 128 ] ] }, { "id": "e214b9ae-ce9a-4d10-9147-1c6aa177fc75", "type": "abstract", "text": [ "OBJECTIVE: To examine the possible association of juvenile idiopathic arthritis (JIA) with polymorphisms within cytokine genes in the Czech population. METHODS: In a case-control study, genotypes of 130 patients with JIA (63 male, 67 female; age at onset 7.6 +/- 4.4 yrs; 43 oligoarticular, 72 polyarticular, 15 systemic form) were compared to 102 healthy unrelated blood donors. Using the polymerase chain reaction technique with sequence-specific primers from the 13th IHWG workshop, we analyzed 19 single nucleotide polymorphisms within 12 different cytokine genes [ interleukin (IL)-1a , IL-1beta , IL-2 , IL-4 , IL-6 , IL-10 , IL-12 , transforming growth factor (TGF)-beta , interferon (IFN)-g ], and related molecules ( IL-1R , IL-1RA , IL-4Ra ). Genotype frequencies were compared using chi-square analysis, and the significance level was corrected for the number of independent tests. RESULTS: Significant positive association was found for the G allele of the IL-4 -1098 T/G polymorphism, which was carried by 10% of cases and 25% of controls [odds ratio (OR) 0.32, 95% confidence interval (CI) 0.16-0.67, corrected p = 0.038). Also, a nonsignificant increase in the frequency of the IL-1beta +3962 C allele was detected in cases (96%) versus controls (84%) (OR 4.65, 95% CI 1.64-13.2, corrected p = 0.091). We did not replicate previously found associations with the IL-1a , IL-6 , IL-10 , and IL-1R IL-1RA polymorphisms. CONCLUSION: Our study showed association with JIA for the IL-4 -1098 T/G polymorphism. It also underlines the genetic contribution of IL-1 polymorphisms to the pathogenesis of JIA, as another polymorphism within the IL-1beta may influence the risk of the disease." ], "offsets": [ [ 129, 1853 ] ] } ]

[ { "id": "af923b8e-fe26-4473-8803-3c08d41c1c7d", "type": "gene", "text": [ "interleukin (IL)-1a" ], "offsets": [ [ 699, 718 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "3552" } ] }, { "id": "2ed19056-ee6a-467b-88eb-c6754ba7e59c", "type": "gene", "text": [ "IL-1beta" ], "offsets": [ [ 722, 730 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "3553" } ] }, { "id": "686b4ae0-4cac-4abc-b07c-2f87905d9381", "type": "gene", "text": [ "IL-2" ], "offsets": [ [ 734, 738 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "3558" } ] }, { "id": "e2ac5dad-3f41-466f-a8be-f7c3c05c19a9", "type": "gene", "text": [ "IL-4" ], "offsets": [ [ 742, 746 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "3565" } ] }, { "id": "177bb61c-9d1e-442b-befb-c691dcaa4b96", "type": "gene", "text": [ "IL-6" ], "offsets": [ [ 750, 754 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "3569" } ] }, { "id": "a0d77636-4559-4ef1-a0b8-59ce0a0fbd20", "type": "gene", "text": [ "IL-10" ], "offsets": [ [ 758, 763 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "3586" } ] }, { "id": "efb5452b-a66c-4271-ab61-fb6102f7e525", "type": "gene", "text": [ "IL-12" ], "offsets": [ [ 767, 772 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "No" } ] }, { "id": "0c0948fd-dcb0-452c-a654-a95964659643", "type": "gene", "text": [ "transforming growth factor (TGF)-beta" ], "offsets": [ [ 776, 813 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "7040" } ] }, { "id": "958c8624-65fe-41e2-83d5-24b2b5a29a23", "type": "gene", "text": [ "interferon (IFN)-g" ], "offsets": [ [ 817, 835 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "No" } ] }, { "id": "a97c5505-1a78-4269-bb98-d4c91002f90c", "type": "gene", "text": [ "IL-1R" ], "offsets": [ [ 863, 868 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "3554" } ] }, { "id": "0895fa45-069e-4882-87b9-2f8a7ad50a11", "type": "gene", "text": [ "IL-1RA" ], "offsets": [ [ 872, 878 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "3557" } ] }, { "id": "05633bc9-9af6-4f74-8708-1b300551db7a", "type": "gene", "text": [ "IL-4Ra" ], "offsets": [ [ 882, 888 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "3566" } ] }, { "id": "947ad686-7d21-490f-a007-ed6b7f91897e", "type": "gene", "text": [ "IL-4" ], "offsets": [ [ 742, 746 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "3565" } ] }, { "id": "e4f3f499-8d71-44e3-aafd-7b9901f4ce77", "type": "gene", "text": [ "IL-1beta" ], "offsets": [ [ 722, 730 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "3553" } ] }, { "id": "5528af4e-785e-47f6-88ff-ba2e50403008", "type": "gene", "text": [ "IL-1a" ], "offsets": [ [ 1525, 1530 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "3552" } ] }, { "id": "5b18a7b8-a92b-4928-bcc2-17c3f2991f53", "type": "gene", "text": [ "IL-6" ], "offsets": [ [ 750, 754 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "3569" } ] }, { "id": "1484bc39-e082-4deb-a038-da9b82fba015", "type": "gene", "text": [ "IL-10" ], "offsets": [ [ 758, 763 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "3586" } ] }, { "id": "d61e3370-c68d-4ba6-b451-66913ac392ce", "type": "gene", "text": [ "IL-1R" ], "offsets": [ [ 863, 868 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "3554" } ] }, { "id": "0cd47e80-800b-4f92-9aca-a5759045c592", "type": "gene", "text": [ "IL-1RA" ], "offsets": [ [ 872, 878 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "3557" } ] }, { "id": "a946b974-04ef-4b20-b2f5-d51b0a0fcbef", "type": "gene", "text": [ "IL-4" ], "offsets": [ [ 742, 746 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "3565" } ] }, { "id": "864e3a8d-612a-4fda-9673-cdb7abae77f5", "type": "gene", "text": [ "IL-1beta" ], "offsets": [ [ 722, 730 ] ], "normalized": [ { "db_name": "NCBI Gene", "db_id": "3553" } ] }, { "id": "2866649e-60d1-4347-9995-4132a040a998", "type": "variant", "text": [ "-1098 T/G" ], "offsets": [ [ 1116, 1125 ] ], "normalized": [ { "db_name": "HGVS-like", "db_id": "T-1098G" } ] }, { "id": "59db1f4d-6219-4617-a9cf-a068c8d5039c", "type": "variant", "text": [ "+3962 C" ], "offsets": [ [ 1348, 1355 ] ], "normalized": [ { "db_name": "HGVS-like", "db_id": "3962C" } ] }, { "id": "9c1fcdd6-4cb6-41c9-bb48-4ed9b84d2991", "type": "variant", "text": [ "-1098 T/G" ], "offsets": [ [ 1116, 1125 ] ], "normalized": [ { "db_name": "HGVS-like", "db_id": "T-1098G" } ] } ]

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