Apolipoprotein E polymorphism affects carotid artery atherosclerosis in smoking hypertensive men.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
The findings suggest that the 4 carriers are particularly susceptible to the atherogenic effects of smoking. This interaction is particularly clear in hypertensive subjects.
Karvonen
Jarkko
J
Department of Internal Medicine, University of Oulu, PO Box 5000, FIN-90014, Finland. jakarvon@paju.oulu.fi
Kauma
Heikki
H
Kervinen
Kari
K
Ukkola
Olavi
O
Rantala
Maire
M
Päivänsalo
Markku
M
Savolainen
Markku J
MJ
Kesäniemi
Y Antero
YA
D000328:Adult; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D002340:Carotid Artery Diseases / Q000209:etiology*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D006973:Hypertension / Q000000981:diagnostic imaging / Q000235:genetics*; D002537:Intracranial Arteriosclerosis / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012907:Smoking / Q000009:adverse effects*; D017539:Tunica Intima / Q000000981:diagnostic imaging; D017540:Tunica Media / Q000000981:diagnostic imaging; D014463:Ultrasonography
D053327:Apolipoprotein E4; D001057:Apolipoproteins E