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


CONCLUSIONS
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.
Ward
Heather
H
Medical Research Council (MRC) Centre for Nutritional Epidemiology in Cancer Prevention and Survival, Institute of Public Health, University of Cambridge, Cambridge, England. heather.ward@srl.cam.ac.uk
Mitrou
Panagiota N
PN
Bowman
Richard
R
Luben
Robert
R
Wareham
Nicholas J
NJ
Khaw
Kay-Tee
KT
Bingham
Sheila
S
D000328:Adult; D000368:Aged; D000483:Alleles; D001057:Apolipoproteins E / Q000235:genetics*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003327:Coronary Disease / Q000097:blood / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006580:Genetic Carrier Screening; D005838:Genotype; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood
D001057:Apolipoproteins E; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D014280:Triglycerides