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Association of gene polymorphisms with coronary artery disease in individuals with or without nonfamilial hypercholesterolemia

      Abstract

      A substantial proportion of individuals with coronary artery disease (CAD) has concomitant hypercholesterolemia. A large-scale association study was performed to identify separately genes that confer susceptibility to CAD in the absence or presence of nonfamilial hypercholesterolemia. The study population comprised 5248 unrelated Japanese individuals, including 3085 subjects with CAD (2350 men, 735 women) and 2163 controls (1329 men, 834 women). Among all study subjects, 2541 individuals (1688 men, 853 women) had nonfamilial hypercholesterolemia, and 2707 individuals (1991 men, 716 women) did not have this condition. The genotypes for 33 polymorphisms of 27 candidate genes were determined with a fluorescence- or colorimetry-based allele-specific DNA primer–probe assay system. Multivariate logistic regression analysis with adjustment for age, body mass index, and the prevalence of smoking, hypertension, diabetes mellitus, and hyperuricemia revealed that three polymorphisms [994G → T (Val279Phe) in the platelet-activating factor acetylhydrolase gene, 242C → T (His72Tyr) in the NADH/NADPH oxidase p22 phox gene, and 1100C → T in the apolipoprotein C-III gene] were significantly associated with CAD in men with hypercholesterolemia. Genotyping of these three polymorphisms may prove informative for prediction of the genetic risk for CAD in men with nonfamilial hypercholesterolemia.

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      References

        • McGovern P.G.
        • Pankow J.S.
        • Shahar E.
        • Doliszny K.M.
        • Folson A.R.
        • Blackburn H.
        • et al.
        Recent trends in acute coronary heart disease. Mortality, morbidity, medical care, and risk factors.
        N. Engl. J. Med. 1996; 334: 884-890
        • Gensini G.F.
        • Comeglio M.
        • Colella A.
        Classical risk factors and emerging elements in the risk profile for coronary artery disease.
        Eur. Heart J. 1998; 19: A53-A61
        • Marenberg M.E.
        • Risch N.
        • Berkman L.F.
        • Floderus B.
        • de Faire U.
        Genetic susceptibility to death from coronary heart disease in a study of twins.
        N. Engl. J. Med. 1994; 330: 1041-1046
        • Lindpaintner K.
        • Pfeffer M.A.
        • Kreutz R.
        • Stampfer M.J.
        • Grodstein F.
        • LaMotte F.
        • et al.
        A prospective evaluation of an angiotensin-converting-enzyme gene polymorphism and the risk of ischemic heart disease.
        N. Engl. J. Med. 1995; 332: 706-711
        • O’Malley J.P.
        • Maslen C.L.
        • Illingworth D.R.
        Angiotensin-converting enzyme DD genotype and cardiovascular disease in heterozygous familial hypercholesterolemia.
        Circulation. 1998; 97: 1780-1783
        • Lu H.
        • Higashikata T.
        • Inazu A.
        • Nohara I.
        • Yu W.
        • Shimizu M.
        • et al.
        Association of estrogen receptor-α gene polymorphisms with coronary artery disease in patients with familial hypercholesterolemia.
        Arterioscler. Thromb. Vasc. Biol. 2002; 22: 821-827
        • Sala G.
        • Di Castelnuovo A.
        • Cuomo L.
        • Gattone M.
        • Giannuzzi P.
        • Iacoviello L.
        • et al.
        The E27 β-adrenergic receptor polymorphism reduces the risk of myocardial infarction in dyslipidemic young males.
        Thromb. Haemostas. 2001; 85: 231-233
        • Jormsjö S.
        • Whatling C.
        • Walter D.H.
        • Zeiher A.M.
        • Hamsten A.
        • Eriksson P.
        Allele-specific regulation of matrix metalloproteinase-7 promoter activity is associated with coronary artery lumen dimensions among hypercholesterolemic patients.
        Arterioscler. Thromb. Vasc. Biol. 2001; 21: 1834-1839
        • Yamada Y.
        • Izawa H.
        • Ichihara S.
        • Takatsu F.
        • Ishihara H.
        • Hirayama H.
        • et al.
        Prediction of the risk of myocardial infarction from polymorphisms in candidate genes.
        N. Engl. J. Med. 2002; 347: 1916-1923
        • Ross R.
        The pathogenesis of atherosclerosis: a perspective for the 1990s.
        Nature. 1993; 362: 801-809
        • Honda Z.
        • Nakamura M.
        • Miki I.
        • Minami M.
        • Watanabe T.
        • Seyama Y.
        • et al.
        Cloning by functional expression of platelet-activating factor receptor from guinea-pig lung.
        Nature. 1991; 349: 342-346
        • Mueller H.W.
        • Haught C.A.
        • McNatt J.M.
        • Cui K.
        • Gaskell S.J.
        • Johnston D.A.
        • et al.
        Measurement of platelet-activating factor in a canine model of coronary thrombosis and in endarterectomy samples from patients with advanced coronary artery disease.
        Circ. Res. 1995; 77: 54-63
      1. Prescott SM, Patel KD, Smiley PL, Stafforini DM, Lorant DE, Zimmerman GA, et al. Potential roles for oxidized phospholipids in inflammation and atherogenesis. In: Weber PC, Leaf A, editors. Atherosclerosis review, vol. 25. New York: Raven Press; 1993. p. 59–68.

        • Stafforini D.M.
        • McIntyre T.M.
        • Carter M.E.
        • Prescott S.M.
        Human plasma platelet-activating factor acetylhydrolase. Association with lipoprotein particles and role in the degradation of platelet-activating factor.
        J. Biol. Chem. 1987; 262: 4215-4222
        • Stremler K.E.
        • Stafforini D.M.
        • Prescott S.M.
        • McIntyre T.M.
        Human plasma platelet-activating factor acetylhydrolase, oxidatively fragmented phospholipids as substrates.
        J. Biol. Chem. 1991; 266: 11095-11103
        • Stafforini D.M.
        • Zimmerman G.A.
        • McIntyre T.M.
        • Prescott S.M.
        The platelet-activating factor acetylhydrolase from human plasma prevents oxidative modification of low-density lipoprotein.
        Trans. Assoc. Am. Physicians. 1992; 105: 44-63
        • Steinberg D.
        • Parthasarathy S.
        • Carew T.E.
        • Khoo J.C.
        • Witztum J.L.
        Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity.
        N. Engl. J. Med. 1989; 320: 915-924
        • Stafforini D.M.
        • Satoh K.
        • Atkinson D.L.
        • Tjoelker L.W.
        • Eberhardt C.
        • Yoshida H.
        • et al.
        Platelet-activating factor acetylhydrolase deficiency. A missense mutation near the active site of an anti-inflammatory phospholipase.
        J. Clin. Invest. 1996; 97: 2784-2791
        • Yamada Y.
        • Ichihara S.
        • Fujimura T.
        • Yokota M.
        Identification of the G994 → T missense mutation in exon 9 of the plasma platelet-activating factor acetylhydrolase gene as an independent risk factor for coronary artery disease in Japanese men.
        Metabolism. 1998; 47: 177-181
        • Hiramoto M.
        • Yoshida H.
        • Imaizumi T.
        • Yoshimizu N.
        • Satoh K.
        A mutation in plasma platelet-activating factor acetylhydrolase (Val279 → Phe) is a genetic risk factor for stroke.
        Stroke. 1997; 28: 2417-2420
        • Unno N.
        • Nakamura T.
        • Kaneko H.
        • Uchiyama T.
        • Yamamoto N.
        • Sygatani J.
        • et al.
        Plasma platelet-activating factor acetylhydrolase deficiency is associated with atherosclerotic occlusive disease in Japan.
        J. Vasc. Surg. 2000; 32: 263-267
        • Griendling K.K.
        • Sorescu D.
        • Ushio-Fukai M.
        NAD(P)H oxidase. Role in cardiovascular biology and disease.
        Circ. Res. 2000; 86: 494-501
        • Azumi H.
        • Inoue N.
        • Takeshita S.
        • Rikitake Y.
        • Kawashima S.
        • Hayashi Y.
        • et al.
        Expression of NADH/NADPH oxidase p22phox in human coronary arteries.
        Circulation. 1999; 100: 1494-1498
        • Inoue N.
        • Kawashima S.
        • Kanazawa K.
        • Yamada S.
        • Akita H.
        • Yokoyama M.
        Polymorphism of the NADH/NADPH oxidase p22 phox gene in patients with coronary artery disease.
        Circulation. 1998; 97: 135-137
        • Guzik T.J.
        • West N.E.J.
        • Black E.
        • McDonald D.
        • Ratnatunga C.
        • Pillai R.
        • et al.
        Functional effect of the C242T polymorphism in the NAD(P)H oxidase p22phox gene on vascular superoxide production in atherosclerosis.
        Circulation. 2000; 102: 1744-1747
        • Ito Y.
        • Azrolan N.
        • O’Connel A.
        • Walsh A.
        • Breslow J.L.
        Hypertriglyceridemia as a result of human apo CIII gene expression in transgenic mice.
        Science. 1990; 249: 790-793
        • Shoulders C.C.
        • Harry P.J.
        • Lagrost L.
        • White S.E.
        • Shah N.F.
        • North J.D.
        • et al.
        Variation at the apo AI/CIII/AIV gene complex is associated with elevated plasma levels of apo CIII.
        Atherosclerosis. 1991; 87: 239-247
        • Bainton D.
        • Miller N.E.
        • Bolton C.H.
        • Yarnell J.W.
        • Sweetnam P.M.
        • Baker I.A.
        • et al.
        Plasma triglyceride and high density lipoprotein cholesterol as predictors of ischaemic heart disease in British men. The Caerphilly and Speedwell collaborative heart disease studies.
        Br. Heart J. 1992; 68: 60-66
        • Waterworth D.W.
        • Talmud P.J.
        • Bujac S.R.
        • Fisher R.M.
        • Miller G.J.
        • Humphries S.E.
        Contribution of apolipoprotein C-III gene variants to determination of triglyceride levels and interaction with smoking in middle-aged men.
        Arterioscler. Thromb. Vasc. Biol. 2000; 20: 2663-2669
        • Tas S.
        • Abdella N.A.
        Blood pressure, coronary artery disease, and glycaemic control in type 2 diabetes mellitus: relation to apolipoprotein-CIII gene polymorphism.
        Lancet. 1994; 343: 1194-1195