Genetic Analysis of Adiponectin Variation and its Association with Type 2 Diabetes in African Americans

OBJECTIVE Adiponectin is an adipocytokine that has been implicated in a variety of metabolic disorders, including T2D and cardiovascular disease. Studies evaluating genetic variants in ADIPOQ have been contradictory when testing association with T2D in different ethnic groups. DESIGN AND METHODS In this study, 18 SNPs in ADIPOQ were tested for association with plasma adiponectin levels and diabetes status. SNPs were examined in two independent African-American cohorts (nmax = 1,116) from the Insulin Resistance Atherosclerosis Family Study (IRASFS) and the African American-Diabetes Heart Study (AA-DHS). RESULTS Five polymorphisms were nominally associated with plasma adiponectin levels in the meta-analysis (P = 0.035-1.02 × 10(-6) ) including a low frequency arginine to cysteine mutation (R55C) which reduced plasma adiponectin levels to <15% of the mean. Variants were then tested for association with T2D in a meta-analysis of these and the Wake Forest T2D case-control study (n = 3,233 T2D, 2645 non-T2D). Association with T2D was not observed (P ≥ 0.08), suggesting limited influence of ADIPOQ variants on T2D risk. CONCLUSIONS Despite identification of variants associated with adiponectin levels, a detailed genetic analysis of ADIPOQ revealed no association with T2D risk. This puts into question the role of adiponectin in T2D pathogenesis: whether low adiponectin levels are truly causal for or rather a consequence.