Abstract
A number of studies have shown that coronary artery disease severity is associated with the ε2/ε3/ε4 polymorphism in the coding region of the apolipoprotein E gene. In this study, we investigated whether the severity of the disease was also influenced by a functional polymorphism (−219 G>T) in the promoter of the gene, and if so, whether the effects of the two polymorphisms were independent. A cohort of 1170 patients with angiographically documented coronary artery disease were genotyped for the two polymorphisms. The frequency of the ε4 allele of the ε2/ε3/ε4 polymorphism increased linearly with increasing number of diseased vessels, so did the −219T allele of the −219 G>T polymorphism. In the sample as a whole, logistic regression analyses indicated that compared with the G/G genotype, the T/T genotype conferred an odds ratio of 1.598 (95% CI=1.161–2.201, P=0.004) in favor of increased disease severity, and the relationship remained significant after adjustment for ε2/ε3/ε4 polymorphism genotypes, plasma cholesterol and triglyceride levels, and other risk factors. The effect of the T/T genotype on disease severity was more significant in patients who did not carry the ε4 allele (OR=1.510, 95% CI=1.028–2.221) than in ε4 allele carriers (OR=1.303, 95% CI=0.619–2.742). There was considerable linkage disequilibrium between the two polymorphisms (ρ=0.9, P<0.001). Logistic regression analysis showed that the −219T-ε4 haplotype conferred an odds ratio of 1.488 (95% CI=1.133–1.954). These findings suggest that the −219 G>T and ε2/ε3/ε4 polymorphisms, which may affect respectively the quantity and quality of apoE, have independent and possibly additive effects on coronary artery disease severity.
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This work was supported by the British Heart Foundation (PG98/183).
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Ye, S., Dunleavey, L., Bannister, W. et al. Independent effects of the −219 G>T and ε2/ε3/ε4 polymorphisms in the apolipoprotein E gene on coronary artery disease: The Southampton Atherosclerosis Study. Eur J Hum Genet 11, 437–443 (2003). https://doi.org/10.1038/sj.ejhg.5200983
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DOI: https://doi.org/10.1038/sj.ejhg.5200983
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