Adiponectin Isoform Patterns in Ethnic-Specific ADIPOQ Mutation Carriers: The IRAS Family Study

Objective: Adiponectin is found in human serum in three groups of multimers (high molecular weight [HMW], medium molecular weight [MMW], and low molecular weight [LMW]). Two ethnic-specific variants in ADIPOQ, G45R (Hispanic-Americans) and R55C (African-Americans), were previously reported. Although carriers of both variants had mean adiponectin levels ≤ 20% of those of noncarriers, they were not clinically different from noncarriers. To compare carriers of both variants and noncarriers, relative quantification of adiponectin isoforms to total adiponectin was performed on serum samples. Methods: The multimeric patterns of serum adiponectin in G45R carriers (n = 23), R55C carriers (n = 3), and Hispanic- and African-American noncarriers (n = 84 and 44, respectively) from the Insulin Resistance Atherosclerosis Family Study were explored using native Western blotting and densitometry. Results: Serum samples from carriers showed an absence of the HMW isoform and a marked reduction in the MMW isoform but an approximate twofold increase in the amount of the LMW isoform. Thus, individuals making only LMW adiponectin are metabolically normal. Conclusions: The results contrast with the proposed biological importance of the HMW multimer. This suggests that the LMW isoform may functionally compensate for some of the loss or reduction of the higher-order multimers in carriers of the G45R and R55C mutations.