Apolipoprotein E polymorphism affects carotid artery atherosclerosis in smoking hypertensive men

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Abstract
Smoking is a risk factor for increased carotid artery intima-media thickness (IMT). The apolipoprotein E (apoE) 4 allele has been associated with cardiovascular diseases, but the role of apoE in regard to intima-media thickness (IMT) has remained controversial. The objective was to investigate whether there is some gene-environment interaction between smoking and apoE polymorphism. DESIGN Cross-sectional case-control study. IMTs of 511 hypertensive and control men were measured ultrasonographically and the apoE genotypes were determined. Genotypes with the 4 allele were pooled into one group and the genotypes without it into another. A significant interaction between the 4 allele and smoking affecting IMT was observed among the hypertensive smokers, as assessed by analysis of covariance. The mean carotid IMT was significantly greater (1.01 versus 0.90 mm, P = 0.003) in the 4 carriers than in the subjects without 4 among the hypertensive smokers. The number of plaques was also significantly higher. No differences were found in the other subjects (hypertensive non-smokers or controls). Linear regression analysis indicated that the 4 allele was an independent determinant of IMT in the hypertensive smokers but not in the other subjects. The estimated average effect of the 4 allele on the mean IMT in the hypertensive smokers was 0.088 mm (P < 0.001). In the oldest age group, the interaction of smoking and 4 was also seen in the control subjects. The findings suggest that the 4 carriers are particularly susceptible to the atherogenic effects of smoking. This interaction is particularly clear in hypertensive subjects.

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