Polymorphisms of ADIPOR1 and ADIPOR2 are associated with phenotypes of type 2 diabetes in Koreans

Abstract

Adiponectin receptors 1 and 2 (ADIPOR1 and ADIPOR2) are considered as candidate genes for type 2 diabetes because they mediate the metabolic effects of adiponectin on target tissues. We investigated whether common polymorphisms of ADIPOR1 and ADIPOR2 are associated with type 2 diabetes or its related phenotypes in Koreans. By sequencing of the DNA samples from 24 unrelated Korean subjects, we selected seven single nucleotide polymorphisms (SNPs) from ADIPOR1 and four SNPs from ADIPOR2 for genotyping in 757 type 2 diabetic patients and 644 nondiabetic subjects. None of the SNPs were associated with the risk of type 2 diabetes. However, g.-7309A > G (rs75172865) in ADIPOR1 was associated with lower insulin resistance, measured by the homeostasis model assessment of insulin resistance (HOMA-IR). Thereafter, we transfected three different human cell lines with plasmids harbouring g.-7309A > G and found that this variant reduced the promoter activity of ADIPOR1. In ADIPOR2, g.-63442G (novel SNP) and g.33447T (rs1044471) were associated with smaller waist circumference. None of the SNPs in either ADIPOR1 or ADIPOR2 were associated with the risk of type 2 diabetes in Koreans. However, the altered activity of the ADIPOR1 promoter was associated with insulin resistance and SNPs of ADIPOR2 were associated with waist circumference.