CETP gene is the only lipid-metabolism gene whose HDL-C association shifts with menopause in the ARIC Study (Atherosclerosis 2008)

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 TaqIB), 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 in 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. Postmenopausal 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 postmenopausally) 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 on plasma lipids of some common genetic polymorphisms that regulate lipoprotein metabolism.