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Diabet Med DOI:10.1111/j.1464-5491.2012.03662.x

Common variants in genes encoding adiponectin (ADIPOQ) and its receptors (ADIPOR1/2), adiponectin concentrations, and diabetes incidence in the Diabetes Prevention Program.

Publication TypeJournal Article
Year of Publication2012
AuthorsMather, KJ, Christophi, CA, Jablonski, KA, Knowler, WC, Goldberg, RB, Kahn, SE, Spector, T, Dastani, Z, Waterworth, D, Richards, JB, Funahashi, T, Pi-Sunyer, FX, Pollin, TI, Florez, JC, Franks, PW
Corporate AuthorsDiabetes Prevention Program Research Group
JournalDiabet Med
Volume29
Issue12
Pages1579-88
Date Published2012 Dec
ISSN1464-5491
KeywordsAdiponectin, Alleles, Diabetes Mellitus, Type 2, Female, Genetic Variation, Genotype, Humans, Incidence, Insulin Resistance, Male, Obesity, Polymorphism, Single Nucleotide, Proportional Hazards Models, Receptors, Adiponectin
Abstract

AIMS: Baseline adiponectin concentrations predict incident Type 2 diabetes mellitus in the Diabetes Prevention Program. We tested the hypothesis that common variants in the genes encoding adiponectin (ADIPOQ) and its receptors (ADIPOR1, ADIPOR2) would associate with circulating adiponectin concentrations and/or with diabetes incidence in the Diabetes Prevention Program population.

METHODS: Seventy-seven tagging single-nucleotide polymorphisms (SNPs) in ADIPOQ (24), ADIPOR1 (22) and ADIPOR2 (31) were genotyped. Associations of SNPs with baseline adiponectin concentrations were evaluated using linear modelling. Associations of SNPs with diabetes incidence were evaluated using Cox proportional hazards modelling.

RESULTS: Thirteen of 24 ADIPOQ SNPs were significantly associated with baseline adiponectin concentrations. Multivariable analysis including these 13 SNPs revealed strong independent contributions of rs17366568, rs1648707, rs17373414 and rs1403696 with adiponectin concentrations. However, no ADIPOQ SNPs were directly associated with diabetes incidence. Two ADIPOR1 SNPs (rs1342387 and rs12733285) were associated with ∼18% increased diabetes incidence for carriers of the minor allele without differences across treatment groups, and without any relationship with adiponectin concentrations.

CONCLUSIONS:   ADIPOQ SNPs are significantly associated with adiponectin concentrations in the Diabetes Prevention Program cohort. This observation extends prior observations from unselected populations of European descent into a broader multi-ethnic population, and confirms the relevance of these variants in an obese/dysglycaemic population. Despite the robust relationship between adiponectin concentrations and diabetes risk in this cohort, variants in ADIPOQ that relate to adiponectin concentrations do not relate to diabetes risk in this population. ADIPOR1 variants exerted significant effects on diabetes risk distinct from any effect of adiponectin concentrations.

URLhttp://dx.doi.org/10.1111/j.1464-5491.2012.03662.x
DOI10.1111/j.1464-5491.2012.03662.x
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/22443353?dopt=Abstract

Alternate JournalDiabet. Med.
PubMed ID22443353
PubMed Central IDPMC3499646
Grant ListP30 DK017047 / DK / NIDDK NIH HHS / United States
R01 DK072041 / DK / NIDDK NIH HHS / United States
U01 DK048489 / DK / NIDDK NIH HHS / United States
DK072041 / DK / NIDDK NIH HHS / United States