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.