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

Abstract

OBJECTIVE: 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. DESIGN AND PATIENTS: 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. RESULTS: 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. CONCLUSIONS: 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.