Genetic and environmental determinants of total and high-molecular weight adiponectin in families with low HDL-cholesterol and early onset coronary heart disease.

Description

This study was undertaken to investigate the heritability and genome-wide linkage analysis of high-molecular weight (HMW) adiponectin as well as to examine the genetic and environmental determinants of the adiponectins and lipid levels, especially HDL cholesterol in Finnish families (n=393 subjects) with coronary heart disease (CHD). The estimates showed high heritability for total adiponectin, HMW adiponectin and also for the HMW/total adiponectin ratio. The partial correlations of the different measures of adiponectin with lipid traits in only unrelated subjects revealed that the strongest correlation was between total adiponectin and HDL cholesterol (r=0.60, p<0.001), with no change after adjusting for body mass index. Moreover, adiponectin had higher environmental than genetic correlations with lipids. Concordantly, the strongest environmental correlation was shown between HDL cholesterol and total adiponectin which is linked with the inverse association observed between the adiponectins and CHD risk in men of this study. As for the genetic correlations, the strongest association detected, even after adjustment for body mass index and statin use, was between HMW adiponectin and LDL cholesterol, which could partly explain the inverse association between HMW adiponectin and the risk of CHD. In addition, univariate linkage analysis of HMW adiponectin showed suggestive evidence of linkage on chromosomes 3q13.2-q24 as well as 6p21 and for total adiponectin on chromosome 11p15. Thus, no significant genetic correlation was detected between HDL cholesterol and the adiponectins which suggest that their levels are probably largely explained by environmental factors and different genes.