Advertisement

Interaction of the glutathione S-transferase genes and cigarette smoking on risk of lower extremity arterial disease: the Atherosclerosis Risk in Communities (ARIC) study

      Abstract

      Glutathione S-transferases M1 or T1 (GSTM1/GSTT1) affect the body's ability either to detoxify or to activate chemicals in cigarette smoke. Cigarette smoking increases the risk of lower extremity arterial disease (LEAD). We conducted a cross-sectional study to evaluate a hypothesized interaction of the genetic polymorphisms of GSTM1 and T1 with cigarette smoking in the risk of LEAD in the ARIC study. A stratified-random sample, including 212 LEAD cases (ankle-brachial index <0.9 in men or <0.85 in women) and 1277 non-cases, was selected from the ARIC cohort of 12 041 middle-aged participants free of CHD, transient ischemic attack and stroke at baseline (1987–1989). Overall, the differences in the frequencies of GSTM1-0 and GSTT1-0 (the homozygous deletion genotype) were not statistically significant between cases and non-cases (44 vs. 41% and 28 vs. 18%). However, smoking was more prevalent among LEAD cases than non-cases. The results suggest that the non-deletion genotype GSTM1-1 interacts with smoking to increase the risk of LEAD, but this interaction was not statistically significant. The functional genotype GSTT1-1 was significantly associated with increased risk of LEAD given smoking after adjustment for other risk factors. In individuals with GSTT1-1, the odds ratios (ORs) (95% confidence intervals) of LEAD were 3.6 (1.4, 9.0) for current smoking and 5.0 (1.9, 13.0) for 20+ pack-years. However, in those with GSTT1-0, the ORs were 0.8 (0.2, 2.8) for current smoking and 0.6 (0.1, 2.1) for 20+ pack-years. The interaction was significant (P<0.05) on the additive scale for current smoking and on both the additive and multiplicative scales for 20+ pack-years. Among non-smokers, GSTT1-1 was not associated with LEAD. The results suggest that the GSTT1-1 polymorphism may be a susceptibility factor modifying the risk of LEAD associated with cigarette smoking.

      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

        • Myers K.A.
        Relationship of smoking to peripheral arterial disease.
        Aust. Family Phys. 1979; 8: 765-768
        • Kannel W.B.
        • McGee D.L.
        Update on some epidemiologic features of intermittent claudication: the Framingham Study.
        J. Am. Geriatr. Soc. 1985; 33: 13-18
        • Lepantalo M.
        • Lassila R.
        Smoking and occlusive peripheral arterial disease. Clinical review.
        Eur. J. Surg. 1991; 157: 83-87
        • Balkau B.
        • Vray M.
        • Eschwege E.
        Epidemiology of peripheral arterial disease.
        J. Cardiovasc. Pharmacol. 1994; 23: S8-16
        • Ogren M.
        • Hedblad B.
        • Janzon L.
        Biased risk factor assessment in prospective studies of peripheral arterial disease due to change in exposure and selective mortality of high-risk individuals.
        J. Cardiovasc. Risk. 1996; 3: 523-528
        • Criqui M.H.
        • Denenberg J.O.
        • Langer R.D.
        • Fronek A.
        The epidemiology of peripheral arterial disease: importance of identifying the population at risk.
        Vasc. Med. 1997; 2: 221-226
        • Fabsitz R.R.
        • Sidawy A.N.
        • Go O.
        • et al.
        Prevalence of peripheral arterial disease and associated risk factors in American Indians: the Strong Heart Study.
        Am. J. Epidemiol. 1999; 149: 330-338
        • Price J.F.
        • Mowbray P.I.
        • Lee A.J.
        • Rumley A.
        • Lowe G.D.
        • Fowkes F.G.
        Relationship between smoking and cardiovascular risk factors in the development of peripheral arterial disease and coronary artery disease: Edinburgh Artery Study.
        Eur. Heart J. 1999; 20: 344-353
        • Schroll M.
        • Munck O.
        Estimation of peripheral arteriosclerotic disease by ankle blood pressure measurements in a population study of 60-year-old men and women.
        J. Chron. Dis. 1981; 34: 261-269
        • Lithell H.
        • Hedstrand H.
        • Karlsson R.
        The smoking habits of men with intermittent claudication.
        Acta Med. Scand. 1975; 197: 473-476
        • Vogt M.T.
        • Wolfson S.K.
        • Kuller L.H.
        Lower extremity arterial disease and the aging process: a review.
        J. Clin. Epidemiol. 1992; 45: 529-542
      1. Zheng ZJ, Barnes RW, Chambless LE, et al. Lower extremity arterial disease estimated by ankle-brachial index in middle-aged black and white men and women: the Atherosclerosis Risk in Communities (ARIC) study. Dissertation. University of North Carolina at Chapel Hill, 1994; 96–129.

        • Guengerich F.P.
        • Thier R.
        • Persmark M.
        • et al.
        Conjugation of carcinogens by theta class glutathione S-transferases: mechanisms and relevance to variations in human risk.
        Pharmacogenetics. 1995; 5: S103-S107
        • Meyer D.J.
        • Coles B.
        • Pemble S.E.
        • Gilmore K.S.
        • Fraser G.M.
        • Ketterer B.
        Theta, a new class of glutathione transferases purified from rat and man.
        Biochem. J. 1991; 274: 409-414
        • Pemble S.
        • Schroeder K.R.
        • Spencer S.R.
        • et al.
        Human glutathione S-transferase theta (GSTT1): cDNA cloning and the characterization of a genetic polymorphism.
        Biochem. J. 1994; 300: 271-276
        • Rebbeck T.R.
        Molecular epidemiology of the human glutathione S-transferase genotypes GSTM1 and GSTT1 in cancer susceptibility.
        Cancer Epidemiol. Biomark. Prev. 1997; 6: 733-743
        • Thier R.
        • Taylor J.B.
        • Pemble S.E.
        • et al.
        Expression of mammalian glutathione S-transferase 5-5 in Salmonella typhimurium TA1535 leads to base-pair mutations upon exposure to dihalomethanes.
        Proc. Nat. Acad. Sci. USA. 1993; 90: 8576-8580
        • 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
        • Pessah-Rasmussen H.
        • Jerntorp P.
        • Stavenow L.
        • et al.
        Eighty-year-old men without cardiovascular disease in the community of Malmo. Part II. Smoking characteristics and ultrasound findings, with special reference to glutathione transferase and pyridoxal-5-phosphate.
        J. Intern. Med. 1990; 228: 17-22
        • Li R.
        • Boerwinkle E.
        • Olshan A.F.
        • et al.
        Glutathione S-transferase genotype as a susceptibility factor in smoking-related coronary heart disease.
        Atherosclerosis. 2000; 149: 451-462
        • The ARIC Investigators
        The Atherosclerosis Risk in Communities (ARIC) Study: design and objectives.
        Am. J. Epidemiol. 1989; 129: 687-702
      2. The ARIC Investigators. Atherosclerosis Risk in Communities Study Protocol, Manual 6. Ultrasound Assessment: Part A. Ultrasound Scanning. ARIC Coordinating Center, Department of Biostatistics, University of North Carolina, 1988.

      3. The ARIC Investigators. Atherosclerosis Risk in Communities Study Protocol 11, Sitting Blood Pressure and Postural Changes in Blood Pressure and Heart Rate. ARIC Coordinating Center, Department of Biostatistics, University of North Carolina, 1988.

      4. Zheng ZJ, Barnes RW, Sharrett AR, et al. Lower extremity arterial disease by ankle-brachial index in black and white men and women: the Atherosclerosis Risk in Communities (ARIC) Study. Abstracts of the 34th Annual Conference on Cardiovascular Disease Epidemiology and Prevention, American Heart Association, Tampa, FL, March 16–17. Circulation 1994;89:12 (P31).

        • Zheng Z.J.
        • Sharrett A.R.
        • Chambless L.E.
        • et al.
        Associations of ankle-brachial index with clinical coronary heart disease, stroke and preclinical carotid and popliteal atherosclerosis: the Atherosclerosis Risk in Communities (ARIC) Study.
        Atherosclerosis. 1997; 131: 115-125
        • Bell D.A.
        • Taylor J.A.
        • Paulson D.F.
        • Robertson C.N.
        • Mohler J.L.
        • Lucier G.W.
        Genetic risk and carcinogen exposure: a common inherited defect of the carcinogen-metabolism gene glutathione S-transferase M1 (GSTM1) that increases susceptibility to bladder cancer.
        J. Nat. Cancer Inst. 1993; 85: 1159-1164
        • Chen H.
        • Sandler D.P.
        • Taylor J.A.
        • et al.
        Increased risk for myelodysplastic syndromes in individuals with glutathione transferase theta 1 (GSTT1) gene defect.
        Lancet. 1996; 347: 295-297
      5. The ARIC Investigators. Atherosclerosis Risk in Communities Study Protocol, Manual 8. Lipid and Lipoprotein Determinations. ARIC Coordinating Center, Department of Biostatistics, University of North Carolina, 1988.

      6. Shah BV, Barnwell BG, Bieler GS. SUDAAN user's manual, Release 7.5. 1997. Research Triangle Park, NC: Research Triangle Institute.

        • Li R.
        • Chambless L.E.
        Test for an additive interaction controlling for covariates by proportional hazards model.
        Am. J. Epidemiol. 1999; 149: S26
        • Hosmer D.W.
        • Lemeshow S.
        Confidence interval estimation of interaction.
        Epidemiology. 1992; 3: 452-456
        • Rothman K.J.
        • Greenland S.
        Modern Epidemiology. 2nd ed. Lippincott-Raven, 1998: 329-342
        • Ross R.
        • Glomset J.A.
        Atherosclerosis and the arterial smooth muscle cell: Proliferation of smooth muscle is a key event in the genesis of the lesions of atherosclerosis.
        Science. 1973; 180: 1332-1339
        • Ross R.
        The pathogenesis of atherosclerosis — an update.
        New Engl. J. Med. 1986; 314: 488-500
        • Ross R.
        Rous-Whipple Award Lecture. Atherosclerosis: a defense mechanism gone awry.
        Am. J. Pathol. 1993; 143: 987-1002
        • Benditt E.P.
        • Benditt J.M.
        Evidence for a monoclonal origin of human atherosclerotic plaques.
        Proc. Nat. Acad. Sci. USA. 1973; 70: 1753-1756
        • Benditt E.P.
        Evidence for a monoclonal origin of human atherosclerotic plaques and some implications.
        Circulation. 1974; 50: 650-652
        • Benditt E.P.
        The origin of atherosclerosis.
        Sci. Am. 1977; 236: 74-85
        • Murry C.E.
        • Gipaya C.T.
        • Bartosek T.
        • Benditt E.P.
        • Schwartz S.M.
        Monoclonality of smooth muscle cells in human atherosclerosis.
        Am. J. Pathol. 1997; 151: 697-705
      7. Hansen ES. International Commission for Protection Against Environmental Mutagens and Carcinogens. ICPEMC Working Paper 7/1/2. Shared risk factors for cancer and atherosclerosis — a review of the epidemiological evidence, Mutat. Res. 1990;239:163–179.

        • Board P.G.
        Biochemical genetics of glutathione-S-transferase in man.
        Am. J. Human Genet. 1981; 33: 36-43
        • Chenevix-Trench G.
        • Young J.
        • Coggan M.
        • Board P.
        Glutathione S-transferase M1 and T1 polymorphisms: susceptibility to colon cancer and age of onset.
        Carcinogenesis. 1995; 16: 1655-1657
        • McWilliams J.E.
        • Sanderson B.J.
        • Harris E.L.
        • Richert-Boe K.E.
        • Henner W.D.
        Glutathione S-transferase M1 (GSTM1) deficiency and lung cancer risk.
        Cancer Epidemiol. Biomark. Prev. 1995; 4: 589-594
        • Seidegard J.
        • Pero R.W.
        • Markowitz M.M.
        • Roush G.
        • Miller D.G.
        • Beattie E.J.
        Isoenzyme(s) of glutathione transferase (class Mu) as a marker for the susceptibility to lung cancer: a follow up study.
        Carcinogenesis. 1990; 11: 33-36
        • Trizna Z.
        • Clayman G.L.
        • Spitz M.R.
        • Briggs K.L.
        • Goepfert H.
        Glutathione S-transferase genotypes as risk factors for head and neck cancer.
        Am. J. Surg. 1995; 170: 499-501
        • Bruning T.
        • Lammert M.
        • Kempkes M.
        • et al.
        Influence of polymorphisms of GSTM1 and GSTT1 for risk of renal cell cancer in workers with long-term high occupational exposure to trichloroethene.
        Arch. Toxicol. 1997; 71: 596-599
        • Their R.
        • Pemble S.E.
        • Kramer H.
        • Taylor J.B.
        • Guengerich F.P.
        • Ketterer B.
        Human glutathione S-transferase T1-1 enhances mutagenicity of 1,2-dibromoethane, dibromomethane and 1,2,3,4-diepoxybutane in Salmonella typhimurium.
        Carcinogenesis. 1996; 17: 163-166
        • Thier R.
        • Muller M.
        • Taylor J.B.
        • Pemble S.E.
        • Ketterer B.
        • Guengerich F.P.
        Enhancement of bacterial mutagenicity of bifunctional alkylating agents by expression of mammalian glutathione S-transferase.
        Chem. Res. Toxicol. 1995; 8: 465-472
        • Mannervik B.
        Glutathione and the evolution of enzymes for detoxictin of products of oxygen metabolism.
        Chem. Scripta. 1986; 26B: 281-284
        • Sies H.
        • Ketterer B.
        Glutathione Conjugation: Mechanisms and Biological Significance. Academic Press, New York1988
        • Ketterer B.
        • Meyer D.J.
        Glutathione transferases: a possible role in the detoxication and repair of DNA and lipid hydroperoxides.
        Mutat. Res. 1989; 214: 33-40
        • Seidegard J.
        • Ekstrom G.
        The role of human glutathione transferases and epoxide hydrolases in the metabolism of xenobiotics.
        Environ. Health Perspect. 1997; 105: 791-799
        • Wiencke J.K.
        • Pemble S.
        • Ketterer B.
        • Kelsey K.T.
        Gene deletion of glutathione S-transferase theta: correlation with induced genetic damage and potential role in endogenous mutagenesis.
        Cancer Epidemiol. Biomark. Prev. 1995; 4: 253-259
        • Greenland S.
        Tests for interaction in epidemiologic studies: a review and a study of power.
        Stat. Med. 1983; 2: 243-251
        • Smith P.G.
        • Day N.E.
        The design of case-control studies: the influence of confounding and interaction effects.
        Int. J. Epidemiol. 1984; 13: 356-365