Abstract

Objective: Adiponectin, a hormone secreted by adipose tissue is of particular interest to metabolic syndrome (MetS), since it is inversely correlated with obesity and insulin sensitivity. However, it is unknown to what extent the genetics of plasma adiponectin and the genetics of obesity and insulin sensitivity are interrelated. We aimed to evaluate the heritability of plasma adiponectin and its genetic correlation with the MetS and MetS related traits and the association between these traits and ten ADIPOQ SNPs.

Research Design and Methods: We made use of a family-based population, the Erasmus Rucphen family (ERF) study (1258 women and 967 men). Heritability analysis was performed using a polygenic model. Genetic correlations were estimated using bivariate heritability analyses. Genetic association analysis was performed using a mixed model.

Results: Plasma adiponectin showed a heritability of 55.1%. Genetic correlation between plasma adiponectin HDL-C and plasma insulin ranged from 15% to 24% but were not significant for fasting glucose, TG, blood pressure, HOMA-IR and CRP. Significant association with plasma adiponectin was found for ADIPOQ variants rs17300539 and rs182052. Nominally significant association was found with plasma insulin and HOMA-IR and ADIPOQ variant rs17300539 after adjusting for plasma adiponectin.

Conclusions: The significant genetic correlation between plasma adiponectin and HDL-C, and plasma insulin should be taken into account in the interpretation of genome wide association studies. Association of ADIPOQ SNPs with plasma adiponectin was replicated and we showed association between one ADIPOQ SNP and plasma insulin and HOMA-IR.