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Genetic Variation in Adiponectin Receptor 1 and Adiponectin Receptor 2 Is Associated With Type 2 Diabetes in the Old Order Amish

¹ Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland
² Geriatric Research and Education Clinical Center, Veterans Administration Medical Center, Baltimore, Maryland

Adiponectin receptor 1 (ADIPOR1) and adiponectin receptor 2 (ADIPOR2) are newly identified receptors for adiponectin, an adipocytokine with anti-inflammatory and insulin-sensitizing properties. We screened for polymorphisms by performing sequence analysis on all eight exons, splice junctions, and 2 kb of the 5' flanking regions of each receptor. We detected 5 single nucleotide polymorphisms (SNPs) in ADIPOR1 and 16 SNPs in ADIPOR2. We genotyped these SNPs in Amish subjects with type 2 diabetes (n = 137), impaired glucose tolerance (IGT) (n = 139), and normal glucose tolerance (n = 342) to test for association with type 2 diabetes. Three intronic SNPs in ADIPOR1 were significantly associated with type 2 diabetes (P = 0.014–0.007; odds ratio [OR] 1.61–1.65) and in high linkage disequilibrium (r² = 0.97–1.0). In ADIPOR2, we found that five SNPs delineated one large haplotype block (r² = 0.9–1.0) spanning >98 kb of the gene and promoter region, which was strongly associated with the combined type 2 diabetes/IGT trait (P 0.001; OR 1.64–1.71). To our knowledge, these data provide the first evidence for association between variation in the adiponectin receptors and type 2 diabetes.

Abbreviations: ADIPOR1, adiponectin receptor 1; ADIPOR2, adiponectin receptor 2; AFDS, Amish Family Diabetes Study; IGT, impaired glucose tolerance; LD, linkage disequilibrium; MAF, minor allele frequency; NGT, normal glucose tolerance; OGTT, oral glucose tolerance test; SNP, single nucleotide polymorphism

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