Triiodothyronine exerts a major pleiotropic effect on reverse cholesterol transport phenotypes

The thyroid hormone triiodothyronine (T₃) is known to be a potent mediator of APOA1 gene expression. With the use of multivariate quantitative genetic analysis, we have assessed the magnitude of shared effects of T₃ on plasma concentrations of apolipoprotein AI (apo AI) and three related phenotypes: HDL-C, apo AII, and LpAI (which is a concentration of apo AI that contains HDL particles). Maximum likelihood techniques were used to simultaneously estimate mean effects and variance components in large, extended Mexican American families living in San Antonio, Tex. We found that T₃ accounted for 16%, 23%, 21%, and 37% of the additive genetic variance in HDL-C, apo AI, apo AII, and LpAI, respectively, while explaining virtually none of the random environmental variance in these phenotypes. T₃ also has a pronounced effect on the pairwise genetic correlations among the four phenotypes: After the pleiotropic effects of T₃ 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 T₃ have a significant effect on HDL-C, apo AI, apo AII, and LpAI and also on the correlations among these phenotypes.