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). Design.-Cross-sectional prevalence study. Setting and Participants.-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 (greater than or equal to 4.14 mmol/L [160 mg/dL]) in women, the epsilon 2 and epsilon 4 alleles were associated with moderately elevated triglyceride values (greater than or equal to 2.82 mmol/L [250 mg/dL]) in men, and the epsilon 2 allele was associated with severely elevated triglyceride values (greater than or equal to 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.