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 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.
Chamberlain
Alanna M
AM
Division of Epidemiology and Community Health, University of Minnesota, School of Public Health, 1300 South 2nd Street, Suite 300, Minneapolis, MN 55454, United States.
Folsom
Aaron R
AR
Schreiner
Pamela J
PJ
Boerwinkle
Eric
E
Ballantyne
Christie M
CM
D000483:Alleles; D001057:Apolipoproteins E / Q000378:metabolism; D050197:Atherosclerosis / Q000235:genetics*; D053480:Cholesterol Ester Transfer Proteins / Q000378:metabolism; D008076:Cholesterol, HDL / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006801:Humans; D008049:Lipase / Q000235:genetics; D008071:Lipoprotein Lipase / Q000235:genetics; D008593:Menopause / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012306:Risk
D001057:Apolipoproteins E; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; C504173:LIPC protein, human; D008049:Lipase; D008071:Lipoprotein Lipase