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 (n(max)=1116) 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=0.035–1.02x10(−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=3233 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.