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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:1829.)
© 2001 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Genetic Control of Coordinated Changes in HDL and LDL Size Phenotypes

David L. Rainwater; Lisa J. Martin; Anthony G. Comuzzie

From the Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, Tex.

Correspondence to David L. Rainwater, PhD, Department of Genetics, Southwest Foundation for Biomedical Research, PO Box 760549, San Antonio, TX 78245-0549. E-mail david{at}darwin.sfbr.org

Abstract—— We investigated the correlation of high density lipoprotein (HDL) and low density lipoprotein (LDL) particle size distributions in samples from >1100 participants in the San Antonio Family Heart Study. By use of analyses of individual correlations of each HDL fraction with each LDL fraction, we devised new metrics for particle size phenotype, termed HDL and LDL, to optimally reflect the size correlations. Confirming previous studies, we found that the 2 size phenotype variables were positively correlated (r=0.51). Quantitative genetic analysis indicated that nearly half (44%) of the variance in HDL and in LDL was explained by the additive effects of genes. Bivariate genetic analyses indicated that a positive genetic correlation (_G=0.56) exists between them and suggested that the pleiotropic effects of a gene or group of genes account for 31% [ie, _G² =(0.56)²=0.31] of the genetic variance in the 2 traits. Triglyceride (TG) levels were negatively related to HDL and LDL, with phenotypic correlations of -0.48 and -0.58, respectively, and genetic correlations of -0.45 and -0.76, respectively, suggesting that genes exert significant pleiotropic effects on the covariation of TGs with each of the size variables. Finally, we evaluated a bivariate model for HDL and LDL in which TG level was included as a covariate. This analysis indicated that a small but significant genetic correlation remains for HDL and LDL, even after accounting for the effects of TGs. Thus, our study demonstrates that the phenotypic correlation of HDL and LDL sizes results in part from the pleiotropic actions of a set of genes, some of which also influence TG levels and some of which do not.

Key Words: LDL size distributions • HDL size distributions • genetics • triglycerides • Mexican Americans

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