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

Alanna M. Chamberlain, Aaron R. Folsom, Pamela J. Schreiner, Eric Boerwinkle, Christie M. Ballantyne

Research output: Contribution to journalArticle

14 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)322-328
Number of pages7
JournalAtherosclerosis
Volume200
Issue number2
DOIs
StatePublished - Oct 1 2008

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Keywords

  • Apolipoprotein E
  • Cholesteryl ester transfer protein
  • HDL
  • Hepatic lipase
  • LDL
  • Lipoprotein lipase
  • Menopause

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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