Submitted to: Clinical Endocrinology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/17/2009
Publication Date: 2/1/2010
Citation: Lamon-Fava, S., Asztalos, B.F., Howard, T., Reboussin, D.M., Horvath, K., Schaefer, E.J., Herrington, D.M. 2010. Association of polymorphisms in genes involved in lipoprotein metabolism with plasma concentrations of remnant lipoproteins and HDL subpopulations before and after hormone therapy in postmenopausal women. Clinical Endocrinology. 72(2):169-75. Interpretive Summary: Recent studies have suggested that women respond differently to hormonal replacement therapy (HT), in relation to plasma lipid levels. Genetic variations in genes that regulate plasma lipid levels may be involved in the plasma lipid response to HT among women. We assessed the effect of HT on plasma levels of two types of lipoproteins: high-density lipoproteins (HDL, also called "good cholesterol"), and remnants of triglyceride-carrying lipoproteins, or RLP, which are considered atherogenic. We found that variation in the estrogen receptor explain part of the variability in lipid response to hormone replacement. However, most of the genes involved in lipid metabolism do not contribute to this variability.
Technical Abstract: A high degree of inter-individual variability in plasma lipid level response to hormone therapy (HT) has been reported. Variations in the estrogen receptor alpha gene (ESR1) and in genes involved in lipid metabolism may explain some of the variability in response to HT. We studied the effect of single nucleotide polymorphisms (SNP) on the HT-related changes in plasma triglycerides (TG), remnant lipoprotein cholesterol (RLP-C), high-density lipoprotein cholesterol (HDL-C) levels, and HDL subpopulations in 208 postmenopausal Caucasian women (N=208) participating in a placebo-controlled randomized trial of 3.2 years of HT. SNPs in ESR1 and in the ATP binding cassette A1 (ABCA1), cholesteryl ester transfer protein (CETP), hepatic lipase (LIPC), lipoprotein lipase (LPL), and scavenger receptor class B type I (SRB1) genes were studied. Carriers of the ESR1 PvuII or IVS1-1505 variants had lower plasma TG concentrations and higher plasma HDL-C and alpha-1 and pre alpha-1 HDL particle levels at baseline and showed greater increases in HDL-C, apo A-I and alpha-1 particle levels after HT than wild-type carriers. Carriers of the N291S and D9N variants in the LPL gene had significantly higher remnant lipoproteins and lower alpha-2 HDL particle levels at baseline. The CETP TaqIB SNP was a significant determinant of baseline plasma HDL-C and HDL subpopulation profile. SNPs in ESR1, CETP and LPL had significant effects on baseline plasma levels of TG-rich and HDL subpopulations. We conclude that, with the exception of ESR1 SNPs, variation in genes involved in lipid metabolism has a very modest effect on lipoprotein response to HT.