TY - JOUR
T1 - Triiodothyronine exerts a major pleiotropic effect on reverse cholesterol transport phenotypes
AU - Comuzzie, Anthony G.
AU - Blangero, J.
AU - Mahaney, Michael C.
AU - Sharp, R. Mark
AU - Vandeberg, John L.
AU - Stern, Michael P.
AU - MacCluer, Jean W.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 1996
Y1 - 1996
N2 - 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.
AB - 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.
KW - HDL-C
KW - LpAI
KW - apo AI
KW - apo AII
KW - thyroid hormones
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U2 - 10.1161/01.ATV.16.2.289
DO - 10.1161/01.ATV.16.2.289
M3 - Article
C2 - 8620345
AN - SCOPUS:0030022059
VL - 16
SP - 289
EP - 293
JO - Arteriosclerosis, Thrombosis, and Vascular Biology
JF - Arteriosclerosis, Thrombosis, and Vascular Biology
SN - 1079-5642
IS - 2
ER -