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

  1. Coleen M. Damcott1,
  2. Sandra H. Ott1,
  3. Toni I. Pollin1,
  4. Laurie J. Reinhart1,
  5. Jian Wang1,
  6. Jeffrey R. O’Connell1,
  7. Braxton D. Mitchell1 and
  8. Alan R. Shuldiner12
  1. 1Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland
  2. 2Geriatric Research and Education Clinical Center, Veterans Administration Medical Center, Baltimore, Maryland
  1. Address correspondence and reprint requests to Alan R. Shuldiner, MD, Division of Endocrinology, DiabetesNutrition, University of Maryland School of Medicine, 660 West Redwood St., Room 494, Baltimore, MD 21201. E-mail: ashuldin{at}medicine.umaryland.edu

Abstract

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.

Footnotes

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