PMID: identifiant
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 (16677372)  |
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Analysis of common PTPN1 gene variants in type 2 diabetes, obesity and associated phenotypes in the French population. |
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| auteur(s) : |
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Claire Cheyssac1, Cécile Lecoeur1, Aurélie Dechaume1, Amina Bibi2, Guillaume Charpentier3, Beverley Balkau4, Michel Marre5, Philippe Froguel1, 2, Fernando Gibson2, Martine Vaxillaire1 |
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| résumé : |
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BACKGROUND: The protein tyrosine phosphatase-1B, a negative regulator for insulin and leptin signalling, potentially modulates glucose and energy homeostasis. PTP1B is encoded by the PTPN1 gene located on chromosome 20q13 showing linkage with type 2 diabetes (T2D) in several populations. PTPN1 gene variants have been inconsistently associated with T2D, and the aim of our study was to investigate the effect of PTPN1 genetic variations on the risk of T2D, obesity and on the variability of metabolic phenotypes in the French population. METHODS: Fourteen single nucleotide polymorphisms (SNPs) spanning the PTPN1 locus were selected from previous association reports and from HapMap linkage disequilibrium data. SNPs were evaluated for association with T2D in two case-control groups with 1227 cases and 1047 controls. Association with moderate and severe obesity was also tested in a case-control study design. Association with metabolic traits was evaluated in 736 normoglycaemic, non-obese subjects from a general population. Five SNPs showing a trend towards association with T2D, obesity or metabolic parameters were investigated for familial association. RESULTS: From 14 SNPs investigated, only SNP rs914458, located 10 kb downstream of the PTPN1 gene significantly associated with T2D (p = 0.02 under a dominant model; OR = 1.43 [1.06-1.94]) in the combined sample set. SNP rs914458 also showed association with moderate obesity (allelic p = 0.04; OR = 1.2 [1.01-1.43]). When testing for association with metabolic traits, two strongly correlated SNPs, rs941798 and rs2426159, present multiple consistent associations. SNP rs2426159 exhibited evidence of association under a dominant model with glucose homeostasis related traits (p = 0.04 for fasting insulin and HOMA-B) and with lipid markers (0.02 = p = 0.04). Moreover, risk allele homozygotes for this SNP had an increased systolic blood pressure (p = 0.03). No preferential transmission of alleles was observed for the SNPs tested in the family sample. CONCLUSION: In our study, PTPN1 variants showed moderate association with T2D and obesity. However, consistent associations with metabolic variables reflecting insulin resistance and dyslipidemia are found for two intronic SNPs as previously reported. Thus, our data indicate that PTPN1 variants may modulate the lipid profile, thereby influencing susceptibility to metabolic disease. |
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| domaine : |
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langue du texte
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Anglais |
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| ISSN : |
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1471-2350 |
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| type de publication : |
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Articles dans des revues avec comité de lecture |
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| DOI : |
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10.1186/1471-2350-7-44 |
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| journal : |
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BMC Medicine Genet |
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| date de publication : |
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2006 |
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| volume : |
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7 |
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| page, identifiant, ... : |
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44 |
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| Descripteur(s) MeSH : |
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Adult – Aged – Case-Control Studies – Diabetes Mellitus – Type 2 – Female – France – Genetic Predisposition to Disease – Humans – Male – Middle Aged – Obesity – Phenotype – Polymorphism – Single Nucleotide – Protein-Tyrosine-Phosphatase – Research Support – Non-U.S. Gov't |
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| contrat, financement : |
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Claire Cheyssac is supported by the Association "200 Familles pour vaincre le Diabète et l'Obésité" and the "Association Française des Diabétiques". This study was supported by grants from the "Region Nord Pas-de-Calais Genopole" and the Lille 2/CNRS institution. |
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