Risk of atherosclerosis: interaction of smoking and glutathione S-transferase genes.
BACKGROUND
Cigarette smoking is a well-known risk factor for not only incident events of coronary heart disease, but also preclinical atherosclerosis. Enzymes including glutathione S-transferase mu (GSTM1) and theta (GSTT1) are involved in the metabolism of tobacco smoke chemicals and are expressed in human vessels and smooth muscle cells.


METHODS
We estimated the effect of interaction of smoking with the deletion polymorphisms of GSTM1 and GSTT1 on the risk of carotid artery atherosclerosis. We analyzed a stratified random sample of 1394 individuals from the Atherosclerosis Risk in Communities (ARIC) study, which is a prospective cohort study of 15,792 white and black men and women randomly selected from four U.S. communities between 1987 and 1989. As an index of generalized atherosclerosis, we used carotid artery intimal-medial thickness, as determined by B-mode ultrasound at the baseline or first follow-up examination in asymptomatic individuals.


RESULTS
We found a suggestion of an interaction between the functional GSTT-1 genotype (GSTT-1) and heavy smoking. For 20 or more pack-years and GSTT1-1, the odds ratio for increased intimal-medial thickness was 4.7 (95% confidence interval = 1.9-11.8); for 20 or more pack-years and GSTT1-0, 1.7 (0.5-5.5); and for nonsmokers and GSTT1-1, 0.7 (0.3-1.5). We found no interaction between smoking and GSTM1.


CONCLUSIONS
The results of this analysis of preclinical atherosclerosis extend reports from the ARIC study of an interaction between smoking and GSTT1-1 in relation to the risk of incident coronary heart disease and lower extremity arterial disease.
Olshan
Andrew F
AF
Department of Epidemiology, School of Public Health, University of North Carolina, Chapel Hill, NC 27599-7435, USA. Andy_Olshan@unc.edu
Li
Rongling
R
Pankow
James S
JS
Bray
Molly
M
Tyroler
Herman A
HA
Chambless
Lloyd E
LE
Boerwinkle
Eric
E
Pittman
Gary S
GS
Bell
Douglas A
DA
D001161:Arteriosclerosis / Q000453:epidemiology* / Q000235:genetics; D002872:Chromosome Deletion; D015331:Cohort Studies; D003327:Coronary Disease / Q000453:epidemiology / Q000235:genetics; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology* / Q000235:genetics
D005982:Glutathione Transferase