Advertisement

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

      Abstract

      We hypothesize that smokers with the null genotype for GSTM1 (GSTM1-0), who thus lack the detoxification enzyme glutathione S-transferase μ1, 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 μ1 develop progression of atherosclerosis at an increased rate.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Atherosclerosis
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Pessah-Rasmussen H.
        • Stavenow L.
        • Seidegard J.
        • Solem J.O.
        • Israelsson B.
        Lack of glutathione transferase activity in intermittent claudication.
        Int. Angiol. 1990; 9: 70-74
        • Rebbeck T.R.
        Molecular epidemiology of the human glutathione S-transferase genotypes GSTM1 and GSTT1 in cancer susceptibility.
        Cancer Epidemiol. Biomarkers Prev. 1997; 6: 733-743
        • Ketterer B.
        • Harris J.M.
        • Talaska G.
        • et al.
        The human glutathione S-transferase supergene family, its polymorphism, and its effects on susceptibility to lung cancer.
        Environ. Health Perspect. 1992; 98: 87-94
        • Mannervik B.
        • Danielson U.H.
        Glutathione transferases-structure and catalytic activity.
        CRC Crit. Rev. Biochem. 1988; 23: 283-337
        • Halliwell B.
        • Gutteridge J.M.C.
        Protection against lipid peroxidation.
        in: Free Radicals in Biology and Medicine. Clarendon Press, Oxford1989: 247-251
        • Bots M.L.
        • de Jong P.T.
        • Hofman A.
        • Grobbee D.E.
        Left, right, near or far wall common carotid intima-media thickness measurements: associations with cardiovascular disease and lower extremity arterial atherosclerosis.
        J. Clin. Epidemiol. 1997; 50: 801-807
        • Smilde T.J.
        • Wollersheim H.
        • VanLangen H.
        • Stalenhoef A.F.H.
        Reproducibility of ultrasonographic measurements of different carotid and femoral artery segments in healthy subjects and in patients with increased intima-media thickness.
        Clin. Sci. 1997; 93: 317-324
        • Kanters S.D.J.M.
        • Algra A.
        • van-Leeuwen M.S.
        • Banga J.D.
        Reproducibility of in vivo carotid intima-media thickness measurements: a review.
        Stroke. 1997; 28: 665-671
        • Touboul P.J.
        • Prati P.
        • Scarabin P.Y.
        • Adrai V.
        • Thibout E.
        • Ducimetiere P.
        Use of monitoring software to improve the measurement of carotid wall thickness by B-mode imaging.
        J. Hypert. 1992; 10 (Supplementary): S37-S41
        • Brockmöller J.
        • Kerb R.
        • Drakoulis N.
        • Nitz M.
        • Roots I.
        Genotype and phenotype of glutathione S-transferase class μ isoenzymes μ and θ in lung cancer patients and controls.
        Cancer Res. 1993; 53: 1004-1011
        • Demacker P.N.M.
        • Hijmans A.G.
        • Vos-Jansen H.E.
        • van't Laar A.
        • Jansen A.P.
        A study of the use of polyethylene glycol in estimating cholesterol in high-density lipoprotein.
        Clin. Chem. 1980; 26: 1775-1779
        • Friedewald W.T.
        • Levy R.I.
        • Fredrickson D.S.
        Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge.
        Clin. Chem. 1972; 18: 499-502
        • Pessah-Rasmussen H.
        • Seidegard J.
        • Stavenow L.
        • Solem J.O.
        • Lindblad B.
        • Xu C.B.
        Glutathione transferase activity in human vessels and in cultured arterial smooth muscle cells.
        Int. Angiol. 1993; 12: 348-354
        • Mooney L.V.A.
        • Bell D.A.
        • Santella R.M.
        • et al.
        Contribution of genetic and nutritional factors to DNA damage in heavy smokers.
        Carcinogenesis. 1997; 18: 503-509
        • Grobbee D.E.
        • Bots M.L.
        Carotid artery intima-media thickness as an indicator of generalized atherosclerosis.
        J. Intern. Med. 1994; 236: 567-573
        • Bots M.L.
        • Hoes A.W.
        • Koudstaal P.J.
        • Hofman A.
        • Grobbee D.E.
        Common carotid intima-media thickness and risk of stroke and myocardial infarction: the Rotterdam Study.
        Circulation. 1997; 96: 1432-1437
        • Heinonen O.P.
        • Albanes D.
        The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers.
        N. Engl. J. Med. 1994; 330: 1029-1035
        • Rapola J.M.
        • Virtamo J.
        • Ripatti S.
        • et al.
        Randomised trial of alpha tocopherol and beta carotene supplements on incidence of major coronary events in men with previous myocardial infarction.
        Lancet. 1997; 349: 1715-1720
        • Stephens N.G.
        • Parsons A.
        • Schofield P.M.
        • et al.
        Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS).
        Lancet. 1996; 347: 781-786
      1. GISSI-Prevenzione I. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial, Lancet 1999; 354: 447–455.

      2. The Heart outcomes prevention evaluation study investigators. Vitamin E supplementation and cardiovascular events in high-risk patients. N Engl J Med 2000; 342: 154–160.