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Atherosclerosis. 2001 Sep;158(1):227-31.

Effect of glutathione S-transferase M1 genotype on progression of atherosclerosis in lifelong male smokers.

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  • 1Division of Human Nutrition and Epidemiology, Wageningen University and Research Center, Dreijenlaan 1, Bodenr 154, 6703 HA Wageningen, The Netherlands. frouwkje.hans@consunet.nl


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.

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