APOE genotype, lipids, and coronary heart disease risk: a prospective population study.

TitleAPOE genotype, lipids, and coronary heart disease risk: a prospective population study.
Publication TypeJournal Article
Year of Publication2009
AuthorsWard, H, Mitrou, PN, Bowman, R, Luben, R, Wareham, NJ, Khaw, K-T, Bingham, S
JournalArch Intern Med
Volume169
Issue15
Pagination1424-9
Date Published2009 Aug 10
ISSN1538-3679
KeywordsAdult, Aged, Alleles, Apolipoproteins E, Cholesterol, HDL, Cholesterol, LDL, Coronary Disease, Female, Follow-Up Studies, Genetic Carrier Screening, Genotype, Humans, Hyperlipidemias, Male, Middle Aged, Proportional Hazards Models, Prospective Studies, Risk Factors, Triglycerides
Abstract

BACKGROUND: The risk of coronary heart disease (CHD) may be related to genetic mutations in the production of apolipoprotein E via alterations to the metabolism of CHD-related blood lipids such as low-density lipoprotein cholesterol and triglycerides.METHODS: The relationship between APOE genotype (*E3/*E3, *E3/*E4, *E2/*E3, *E4/*E4, *E2/*E4, and *E2/*E2) and fatal and nonfatal CHD was examined among 10 035 men and 12 134 women, aged 440 to 79 years, from the Norfolk, England, arm of the European Prospective Into Nutrition and Cancer Study (1993-2007). During an average of 11 years of follow-up, 2712 CHD events were documented.RESULTS: The hazard ratio for CHD was 0.88 (95% confidence interval, 0.77-0.99) for *E2 carriers (*E2/*E2 and *E2/*E3) and 1.09 (1.00-1.19) for *E4 carriers (*E3/*E4 and *E4/*E4) compared with homozygous *E3/*E3 individuals after age and sex adjustment. Similar values were obtained when systolic blood pressure, body mass index, diabetes mellitus, alcohol intake, physical activity, and smoking were added to the model. After additional adjustment for baseline levels of the ratio of low- to high-density lipoprotein cholesterol, the hazard ratios (and 95% confidence intervals) for *E2 and *E4 carriers were 0.97 (0.85-1.10) and 1.06 (0.97-1.15), respectively, when compared with *E3 homozygotes. No interactions by sex, smoking status, or age groups were observed.CONCLUSION: In the largest prospective cohort study to date, CHD risk was not associated with APOE genotype after controlling for a variety of cardiovascular risk factors, particularly the ratio of low- to high-density lipoprotein cholesterol.

DOI10.1001/archinternmed.2009.234
Alternate JournalArch. Intern. Med.
Citation Key10.1001/archinternmed.2009.234
PubMed ID19667307
Grant ListG0401527 / / Medical Research Council / United Kingdom
MC_U106179471 / / Medical Research Council / United Kingdom