Apolipoprotein E alleles, dyslipidemia, and coronary heart disease. The Framingham Offspring Study.
OBJECTIVE
To describe the association between apolipoprotein E alleles (epsilon 2, epsilon 3, and epsilon 4), dyslipidemias, and coronary heart disease (CHD).


METHODS
Cross-sectional prevalence study.


METHODS
Community-based sample of men (n = 1034) and women (n = 916) aged 40 to 77 years who are participating in a long-term study of cardiovascular disease. Study participants underwent fasting lipid measurements, coronary risk factor determinations, and a comprehensive evaluation for the presence of current or previous CHD.


RESULTS
Compared with the epsilon 3 allele, the epsilon 4 allele was associated with elevated low-density lipoprotein cholesterol values (> or = 4.14 mmol/L [160 mg/dL]) in women, the epsilon 2 and epsilon 4 alleles were associated with moderately elevated triglyceride values (> or = 2.82 mmol/L [250 mg/dL]) in men, and the epsilon 2 allele was associated with severely elevated triglyceride values (> or = 5.64 mmol/L [500 mg/dL]) in men. The apolipoprotein E alleles were not associated with hypertension, obesity, smoking, or diabetes, but the epsilon 4 allele frequency was reduced in women after 60 years of age. The age-adjusted prevalence of CHD was associated with the epsilon 4 allele in both men (relative odds = 1.53, P = .04) and women (relative odds = 1.99, P = .05). In analyses for women and for both sexes combined, this relation persisted after adjustment by hypertension, smoking, obesity, diabetes, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol.


CONCLUSIONS
Apolipoprotein E alleles are important genetic markers for dyslipidemia and CHD. The estimated CHD odds associated with the epsilon 4 allele appears to be greater than that for any other known genetic lipid abnormality, and the association of the epsilon 4 allele with CHD remains significant in women and both sexes combined after adjustment by traditional coronary risk factors and lipids.
Wilson
P W
PW
Framingham Heart Study, MA 01701.
Myers
R H
RH
Larson
M G
MG
Ordovas
J M
JM
Wolf
P A
PA
Schaefer
E J
EJ
D000328:Adult; D017677:Age Distribution; D000368:Aged; D000483:Alleles; D001057:Apolipoproteins E / Q000235:genetics*; D008076:Cholesterol, HDL / Q000097:blood; D003327:Coronary Disease / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D003430:Cross-Sectional Studies; D005260:Female; D005819:Genetic Markers; D006801:Humans; D006949:Hyperlipidemias / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D015995:Prevalence; D012307:Risk Factors; D017678:Sex Distribution; D014280:Triglycerides / Q000097:blood
D001057:Apolipoproteins E; D008076:Cholesterol, HDL; D005819:Genetic Markers; D014280:Triglycerides