Adiponectin receptor 1 variants associated with lower insulin resistance in African Americans

Adiponectin has been shown to have a role in insulin resistance. However, little is known about the contribution of genetic variation in the adiponectin receptor 1 gene (ADIPOR1) in this regard. We hypothesized that variation in ADIPOR1 would be associated with significant changes in insulin resistance and tested this hypothesis in a cohort of 483 African-American adolescents. Seven single nucleotide polymorphisms (SNPs) of ADIPOR1 spanning from the promoter to the 3'-untranslated region were genotyped. We analyzed single SNPs and haplotypes for associations with insulin resistance [homeostasis model assessment of insulin resistance (HOMA-IR)] in the full cohort as well as lean (BMI < 85%) and non-lean (BMI >or= 85%) subsets. There was no evidence of ADIPOR1 variant effects on HOMA-IR in the full cohort or in the lean subset. However, in the non-lean subset, SNP +5843 (A allele), and haplotypes including SNPs -8505/-5692/+3002/+5843 (ATTA and AGTG) showed significant associations with decreased HOMA-IR after adjustment for sex, puberty, adiponectin, and waist z-score. Our findings suggest not only that ADIPOR1 variants influence insulin resistance in the presence of adiposity, but also that these variants and haplotypes are protective in African Americans.