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Common Variants in the Adiponectin Gene (ADIPOQ) Associated With Plasma Adiponectin Levels, Type 2 Diabetes, and Diabetes-Related Quantitative Traits

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dc.contributor.author Hivert, Marie-France en_US
dc.contributor.author Manning, Alisa K. en_US
dc.contributor.author McAteer, Jarred B. en_US
dc.contributor.author Florez, Jose C. en_US
dc.contributor.author Dupuis, Josée en_US
dc.contributor.author Fox, Caroline S. en_US
dc.contributor.author O'Donnell, Christopher J. en_US
dc.contributor.author Cupples, L. Adrienne en_US
dc.contributor.author Meigs, James B. en_US
dc.date.accessioned 2011-12-29T22:21:54Z
dc.date.available 2011-12-29T22:21:54Z
dc.date.issued 2011-12-29
dc.identifier.citation Hivert, Marie-France, Alisa K. Manning, Jarred B. McAteer, Jose C. Florez, Josée Dupuis, Caroline S. Fox, Christopher J. O'Donnell, L. Adrienne Cupples, James B. Meigs. "Common Variants in the Adiponectin Gene (ADIPOQ) Associated With Plasma Adiponectin Levels, Type 2 Diabetes, and Diabetes-Related Quantitative Traits" Diabetes 57(12): 3353-3359. (2008) en_US
dc.identifier.issn 1939-327X en_US
dc.identifier.uri http://hdl.handle.net/2144/2572
dc.description.abstract OBJECTIVE: Variants in ADIPOQ have been inconsistently associated with adiponectin levels or diabetes. Using comprehensive linkage disequilibrium mapping, we genotyped single nucleotide polymorphisms (SNPs) in ADIPOQ to evaluate the association of common variants with adiponectin levels and risk of diabetes. RESEARCH DESIGN AND METHODS: Participants in the Framingham Offspring Study (n = 2,543, 53% women) were measured for glycemic phenotypes and incident diabetes over 28 years of follow-up; adiponectin levels were quantified at exam 7. We genotyped 22 tag SNPs that captured common (minor allele frequency >0.05) variation at r2 > 0.8 across ADIPOQ plus 20 kb 5′ and 10 kb 3′ of the gene. We used linear mixed effects models to test additive associations of each SNP with adiponectin levels and glycemic phenotypes. Hazard ratios (HRs) for incident diabetes were estimated using an adjusted Cox proportional hazards model. RESULTS— Two promoter SNPs in strong linkage disequilibrium with each other (r2 = 0.80) were associated with adiponectin levels (rs17300539; Pnominal [Pn] = 2.6 × 10−8; Pempiric [Pe] = 0.0005 and rs822387; Pn = 3.8 × 10−5; Pe = 0.001). A 3′-untranslated region (3′UTR) SNP (rs6773957) was associated with adiponectin levels (Pn = 4.4 × 10−4; Pe = 0.005). A nonsynonymous coding SNP (rs17366743, Y111H) was confirmed to be associated with diabetes incidence (HR 1.94 [95% CI 1.16–3.25] for the minor C allele; Pn = 0.01) and with higher mean fasting glucose over 28 years of follow-up (Pn = 0.0004; Pe = 0.004). No other significant associations were found with other adiposity and metabolic phenotypes. CONCLUSIONS: Adiponectin levels are associated with SNPs in two different regulatory regions (5′ promoter and 3′UTR), whereas diabetes incidence and time-averaged fasting glucose are associated with a missense SNP of ADIPOQ. en_US
dc.description.sponsorship Centre de Recherche Medicale de l'Universite de Sherbrooke; Canadian Institute of Health Research Fellowships Health Professional Award; National Institutes of Health Research Career Award (K23-DK-65978-04); National Institute of Diabetes and Digestive and Kidney Diseases (K24-DK-080140); American Diabetes Association Career Developement Award; Sanofi-Aventis; National Heart, Lung, and Blood Institute's Framingham Heart Study (N01-HC-25195); General Clinical Research Centers Program (M01-RR-01066); National Institutes of Health National Research Resource Center Shared Instrumentation Grant (1S10-RR-163736-01A1) en_US
dc.language.iso en en_US
dc.publisher American Diabetes Association en_US
dc.rights Copyright 2008, American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details. en_US
dc.title Common Variants in the Adiponectin Gene (ADIPOQ) Associated With Plasma Adiponectin Levels, Type 2 Diabetes, and Diabetes-Related Quantitative Traits en_US
dc.type article en_US
dc.identifier.doi 10.2337/db08-0700 en_US
dc.identifier.pubmedid 18776141 en_US
dc.identifier.pmcid 2584143 en_US


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