rs1044471

This case-control association study examined 41 tag and candidate SNPs in the adiponectin (ADIPOQ) and its receptor genes (ADIPOR1, ADIPOR2) in relation to insulin sensitivity measured by euglycemic clamp in 584 white and 119 African American adolescents and their parents (n=703 total). One SNP in ADIPOQ (rs822393, p=0.0034) reached corrected significance threshold in whites and accounted for 1.9% of variance in insulin sensitivity; four additional ADIPOQ SNPs (rs4632532, rs266729, rs182052, rs7649121) showed suggestive associations (p<0.05). Two SNPs in ADIPOR1 showed suggestive associations in African Americans. The results suggest genetic variants in adiponectin pathway genes influence insulin sensitivity, with age potentially modifying the effect.

This association study screened ADIPOR1 and ADIPOR2 genes for mutations in 129 patients with severe insulin resistance, then tested 24 polymorphisms for association with type 2 diabetes in 2,127 case-control participants and metabolic traits in 1,721 population-based subjects. No missense or nonsense mutations were found in the insulin resistance cohort, and no significant associations were detected between any ADIPOR1 or ADIPOR2 SNPs and type 2 diabetes risk or related metabolic traits in UK Europid populations, suggesting these genes are not major contributors to insulin resistance or type 2 diabetes susceptibility.

Candidate gene association study in 439 Mexican Americans examining variants in ADIPOQ, ADIPOR1, and ADIPOR2 genes and insulin resistance syndrome traits. ADIPOQ variants (rs4632532, rs266729) were associated with BMI, fasting insulin, and skinfold thickness. ADIPOR1 rs7539542 was associated with BMI and waist circumference. Notably, 14 ADIPOR2 SNPs were associated with fasting triglycerides, with rs10848569, rs929434, rs3809266, and rs12342 showing strongest associations (p<0.0004) and demonstrating that rs929434 explains 47% of previously detected linkage signal.