Low-density lipoprotein and high-density lipoprotein cholesterol levels in relation to genetic polymorphisms and menopausal status: The Atherosclerosis Risk in Communities (ARIC) Study

Genes coding for proteins involved in lipid metabolism and, in women, menopausal Status are independently associated with high-density lipoprotein cholesterol (HDL-c) and low-density lipoprotein cholesterol (LDL-c) levels. We examined whether the association between common functional genetic polymorphisms of apolipoprotein E (apoE Cys112Arg and Arg158Cys) gene and LDL-c levels, as well as the associations between the cholesteryl ester transfer protein (CETP Taq1B), hepatic lipase (LIPC C-514T). and lipoprotein lipase (LPL Ser447Stop) genes and HDL-c levels are significantly modified by menopausal Status. Plasma lipid concentrations. genotype, and menopausal status were assessed across four examinations ill a sample Of Caucasian and African-American women (n = 4652-4876) who were aged 45-64 years at baseline from the Atherosclerosis Risk in Communities (ARIC) Study. The association between LDL-c levels and the apoE gene, and HDL-c levels and the LIPC and LPL genes were not modified by menopausal status. The only statistically significant gene by menopause interaction was with the CETP gene on HDL-c concentrations (p = 0.04). However, the significant CETP gene by menopause interaction was possibly due to chance because Of multiple testing. Post menopausal women who were carriers of the A allele of the CETP gene had approximately 0.7 mg/dL lower HDL-c levels than pre-/perimenopausal Counterparts. whereas the opposite pattern of HDL-c (0.4 mg/dL higher HDL-c post menopausally) was observed for the GG genotype. Overall, Our data suggest that the decrease in endogenous estrogen as a result of menopause may independently affect lipoprotein concentration. but does not alter the effect oil plasma lipids of some common genetic polymorphisms that regulate lipoprotein metabolism. (C) 2008 Elsevier Ireland Ltd. All rights reserved.