Title | Low-density lipoprotein and high-density lipoprotein cholesterol levels in relation to genetic polymorphisms and menopausal status: the Atherosclerosis Risk in Communities (ARIC) Study. |
Publication Type | Journal Article |
Year of Publication | 2008 |
Authors | Chamberlain AM, Folsom AR, Schreiner PJ, Boerwinkle E, Ballantyne CM |
Journal | Atherosclerosis |
Volume | 200 |
Issue | 2 |
Pagination | 322-8 |
Date Published | 2008 Oct |
ISSN | 1879-1484 |
Keywords | Alleles, Apolipoproteins E, Atherosclerosis, Cholesterol Ester Transfer Proteins, Cholesterol, HDL, Cholesterol, LDL, Female, Genotype, Humans, Lipase, Lipoprotein Lipase, Menopause, Middle Aged, Polymorphism, Genetic, Risk |
Abstract | 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. |
DOI | 10.1016/j.atherosclerosis.2007.12.045 |
Alternate Journal | Atherosclerosis |
PubMed ID | 18275964 |
PubMed Central ID | PMC2583258 |
Grant List | N01HC55020 / HL / NHLBI NIH HHS / United States N01HC55018 / HL / NHLBI NIH HHS / United States N01-HC-55022 / HC / NHLBI NIH HHS / United States N01-HC-55016 / HC / NHLBI NIH HHS / United States N01HC55015 / HL / NHLBI NIH HHS / United States N01 HC055019 / HC / NHLBI NIH HHS / United States N01-HC-55019 / HC / NHLBI NIH HHS / United States N01-HC-55015 / HC / NHLBI NIH HHS / United States N01HC55016 / HL / NHLBI NIH HHS / United States N01HC55019 / HL / NHLBI NIH HHS / United States N01HC55022 / HL / NHLBI NIH HHS / United States N01-HC-55021 / HC / NHLBI NIH HHS / United States 01-HC-55020 / HC / NHLBI NIH HHS / United States N01-HC-55018 / HC / NHLBI NIH HHS / United States N01HC55021 / HL / NHLBI NIH HHS / United States |