Effect of glutathione S-transferase M1 genotype on progression of atherosclerosis in lifelong male smokers.
We hypothesize that smokers with the null genotype for GSTM1 (GSTM1-0), who thus lack the detoxification enzyme glutathione S-transferase mu-1, develop atherosclerosis at an increased rate compared to smokers with the positive genotype (GSTM1-1). We used data from a 2-year randomized placebo-controlled trial on the effect of vitamin E on atherosclerosis among 189 male smokers. Progression of atherosclerosis was measured by 2-year change of the common carotid intima media thickness (CCA-IMT) as measured by B-mode ultrasonography. The frequency of GSTM1-0 genotype was 0.5 in both the placebo and the vitamin E group. Smokers with GSTM1-0 genotype had a tendency to higher baseline CCA-IMT values than those with GSTM1-1 (0.97 versus 0.92 mm, P=0.09). Within the placebo group, more CCA-IMT progression was found for smokers with the GSTM1-0 than for smokers with the GSTM1-1 genotype after adjustment for baseline IMT and major CVD risk factors (0.050 versus -0.002 mm, P=0.046). In the vitamin E group no effect of GSTM1 genotype on atherosclerosis progression was found. Overall, smokers with GSTM1-0 genotype had a higher mean 2-year progression compared to those with GSTM1-1 as shown by a difference in increase of 0.042 mm (95% CI 0.006; 0.078, P=0.02). In conclusion, our data suggest that smokers lacking the detoxifying enzyme GST mu-1 develop progression of atherosclerosis at an increased rate.
de Waart
F G
FG
Division of Human Nutrition and Epidemiology, Wageningen University and Research Center, Dreijenlaan 1, Bodenr 154, 6703 HA Wageningen, The Netherlands. frouwkje.hans@consunet.nl
Kok
F J
FJ
Smilde
T J
TJ
Hijmans
A
A
Wollersheim
H
H
Stalenhoef
A F
AF
D001161:Arteriosclerosis / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D017536:Carotid Artery, Common / Q000000981:diagnostic imaging / Q000473:pathology; D018450:Disease Progression; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects* / Q000235:genetics; D017539:Tunica Intima / Q000473:pathology; D017540:Tunica Media / Q000473:pathology; D014463:Ultrasonography
D005982:Glutathione Transferase