TRIIODOTHYRONINE EXERTS A MAJOR PLEIOTROPIC EFFECT ON REVERSE CHOLESTEROL TRANSPORT PHENOTYPES

The thyroid hormone triiodothyronine (T-3) is known to be a potent med iator Of APOA1 gene expression. With the use of multivariate quantitat ive genetic analysis, we have assessed the magnitude of shared effects of T-3 On plasma concentrations of apolipoprotein AI (ape AI) and thr ee related phenotypes: HDL-C, apo AII, and LpAI (which is a concentrat ion of apo AI that contains HDL particles). Maximum likelihood techniq ues were used to simultaneously estimate mean effects and variance com ponents in large, extended Mexican American families living in San Ant onio, Tex. We found that T-3 accounted for 16%, 23%, 21%, and 37% of t he additive genetic variance in HDL-C, apo AI, apo AII, and LpAI, resp ectively, while explaining virtually none of the random environmental variance in these phenotypes. T-3 also has a pronounced effect on the pairwise genetic correlations among the four phenotypes: After the ple iotropic effects of T-3 concentrations are controlled for, the genetic correlations are reduced by 6% in the case of HDL-C and apo AI and 97 % for apo AII and LpAI. Thus, genes that influence T-3 have a signific ant effect on HDL-C, apo AI, apo AII, and LpAI and also on the correla tions among these phenotypes.