Genetic Analysis of ADIPOR1 and ADIPOR2 Candidate Polymorphisms for Type 2 Diabetes in the Caucasian Population
- Martine Vaxillaire1,
- Aurélie Dechaume1,
- Valérie Vasseur-Delannoy1,
- Saida Lahmidi1,
- Vincent Vatin1,
- Frédéric Leprêtre1,
- Philippe Boutin1,
- Serge Hercberg2,
- Guillaume Charpentier3,
- Christian Dina1 and
- Philippe Froguel14
- 1Centre National de la Recherche Scientifique (CNRS) UMR 8090, Institute of Biology and Pasteur Institute, Lille, France
- 2Scientific and Technical Institute of Nutrition and Food (ISTNA-CNAM), Institut National de la Santé et de la Recherche Médicale (INSERM) U557, INRA U1125, Paris, France
- 3Department of Endocrinology and Diabetology, Centre Hospitalier Sud Francilien, Corbeil-Essonnes, France
- 4Section of Genomic Medicine, Imperial College Genome Centre, Hammersmith Campus, Imperial College London, London, U.K
- Address correspondence and reprint requests to Dr. Martine Vaxillaire, CNRS 8090, Institut de Biologie, Institut Pasteur de Lille, 1 rue du Professeur Calmette, BP 245, 59019 Lille, France. E-mail: martine.vaxillaire{at}pasteur-lille.fr
Abstract
Adiponectin is a metabolic link between adipose tissue and insulin action, mediating part of obesity-associated insulin resistance and type 2 diabetes. Two adiponectin receptors have been identified, and we investigated whether sequence variations in adiponectin receptor 1 (ADIPOR1) and adiponectin receptor 2 (ADIPOR2) genes could contribute to the genetic risk for type 2 diabetes in a case-control study of 1,498 Caucasian subjects. We sequenced the putative functional regions of the two genes in 48 subjects and selected single nucleotide polymorphisms (SNPs) from the public database. Five SNPs in ADIPOR1 and 12 in ADIPOR2 were tested for association with type 2 diabetes. No SNP of ADIPOR1 showed association in any of the samples from the French population. In contrast, three SNPs of ADIPOR2 showed nominal evidence for association with type 2 diabetes before correction for multiple testing (odds ratio [OR] 1.29–1.37, P = 0.034–0.014); only rs767870, located in intron 6, was replicated in an additional diabetes dataset (n = 636, OR 1.29, P = 0.020) with significant allelic association from the overall meta-analysis of 2,876 subjects (adjusted OR 1.25 [95% CI 1.07–1.45], P = 0.0051). In conclusion, our data suggest a modest contribution of ADIPOR2 variants in diabetes risk in the French population.
- AdipoR1, adiponectin receptor 1
- AdipoR2, adiponectin receptor 2
- HWE, Hardy-Weinberg equilibrium
- LD, linkage disequilibrium
- MAF, minor allele frequency
- SNP, single nucleotide polymorphism
- UTR, untranslated region
Footnotes
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
F.L. is currently affiliated with INSERM EA2683, Centre Hospitalier Universitaire de Lille, Lille, France.
Additional information for this article can be found in an online appendix at http://diabetes.diabetesjournals.org.
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- Accepted December 13, 2005.
- Received May 25, 2005.
- DIABETES
