Advertisement

Genetic variations of apolipoprotein A5 gene is associated with the risk of coronary artery disease among Chinese in Taiwan

      Abstract

      Recently, a T/C polymorphism of the promoter region of the APOA5 gene at position -1131 and a G/T polymorphism at position 553 were found to be associated with increased levels of plasma triglyceride. Triglyceride plays a role in coronary artery disease (CAD), so this case–control study tested for a possible link between these two APOA5 polymorphisms, their common haplotypes and the risk of CAD. The subjects included 211 CAD patients and 677 unrelated controls. A significantly higher level of triglycerides and a lower level of high-density lipoprotein cholesterol (HDL-C) were noted for carriers with -1131C than for non-carriers (P < 0.001 and 0.013, respectively) among controls. Plasma triglyceride levels were significantly higher (P = 0.014) in controls with genotypes that contained the c.553T allele than in homozygotes for the G allele. Subjects homozygous for the wild-type haplotype had significantly lower triglyceride levels and higher HDL-C levels than subjects with all other haplotype pairs. The -1131C homozygous carriers and c.553T heterozygous carriers were found more frequently in 211 patients with CAD than in the 317 age/sex-matched controls (P = 0.008 and 0.023, respectively) in univariate analysis. The significant association between c.553T allele carriers with CAD remained in multivariate regression analysis (OR, 1.79; CI, 1.07–3.00; P = 0.028), after adjustments were made for other risk factors. Notably, haplotype analysis further verified that the APOA5 -1131C and c.553T bi-loci haplotype was significantly overpresented in CAD, as compared to the controls. These results indicate that the variants of APOA5 gene modulate plasma triglyceride and may use them to predict CAD susceptibility in Taiwanese Chinese.

      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

        • Hokanson J.E.
        • Austin M.A.
        Plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level: a meta-analysis of population-based prospective studies.
        J Cardiovasc Risk. 1996; 3: 213-219
        • Heller D.A.
        • de F.U.
        • Pedersen N.L.
        • Dahlen G.
        • McClearn G.E.
        Genetic and environmental influences on serum lipid levels in twins.
        N Engl J Med. 1993; 328: 1150-1156
        • Pennacchio L.A.
        • Olivier M.
        • Hubacek J.A.
        • et al.
        An apolipoprotein influencing triglycerides in humans and mice revealed by comparative sequencing.
        Science. 2001; 294: 169-173
        • van d V.
        • Sammels M.G.
        • Leegwater A.C.
        • et al.
        Apolipoprotein A–V: a novel apolipoprotein associated with an early phase of liver regeneration.
        J Biol Chem. 2001; 276: 44512-44520
        • van d V.
        • Schaap F.G.
        • Levels J.H.
        • et al.
        Adenoviral overexpression of apolipoprotein A-V reduces serum levels of triglycerides and cholesterol in mice.
        Biochem Biophys Res Commun. 2002; 295: 1156-1159
        • Nabika T.
        • Nasreen S.
        • Kobayashi S.
        • Masuda J.
        The genetic effect of the apoprotein AV gene on the serum triglyceride level in Japanese.
        Atherosclerosis. 2002; 165: 201-204
        • Endo K.
        • Yanagi H.
        • Araki J.
        • Hirano C.
        • Yamakawa-Kobayashi K.
        • Tomura S.
        Association found between the promoter region polymorphism in the apolipoprotein A-V gene and the serum triglyceride level in Japanese schoolchildren.
        Hum Genet. 2002; 111: 570-572
        • Baum L.
        • Tomlinson B.
        • Thomas G.N.
        APOA5-1131T > C polymorphism is associated with triglyceride levels in Chinese men.
        Clin Genet. 2003; 63: 377-379
        • Lai C.Q.
        • Tai E.S.
        • Tan C.E.
        • et al.
        The APOA5 locus is a strong determinant of plasma triglyceride concentrations across ethnic groups in Singapore.
        J Lipid Res. 2003; 44: 2365-2373
        • Aouizerat B.E.
        • Kulkarni M.
        • Heilbron D.
        • et al.
        Genetic analysis of a polymorphism in the human apoA-V gene: effect on plasma lipids.
        J Lipid Res. 2003; 44: 1167-1173
        • Li G.P.
        • Wang J.Y.
        • Yan S.K.
        • Chen B.S.
        • Xue H.
        • Wu G.
        Genetic effect of two polymorphisms in the apolipoprotein A5 gene and apolipoprotein C3 gene on serum lipids and lipoproteins levels in a Chinese population.
        Clin Genet. 2004; 65: 470-476
        • Pennacchio L.A.
        • Olivier M.
        • Hubacek J.A.
        • Krauss R.M.
        • Rubin E.M.
        • Cohen J.C.
        Two independent apolipoprotein A5 haplotypes influence human plasma triglyceride levels.
        Hum Mol Genet. 2002; 11: 3031-3038
        • Kao J.T.
        • Wen H.C.
        • Chien K.L.
        • Hsu H.C.
        • Lin S.W.
        A novel genetic variant in the apolipoprotein A5 gene is associated with hypertriglyceridemia.
        Hum Mol Genet. 2003; 12: 2533-2539
        • Hsu L.A.
        • Ko Y.L.
        • Hsu K.H.
        • Ko Y.H.
        • Lee Y.S.
        Genetic variations in the cholesteryl ester transfer protein gene and high density lipoprotein cholesterol levels in Taiwanese Chinese.
        Hum Genet. 2002; 110: 57-63
        • Ko Y.L.
        • Ko Y.S.
        • Wang S.M.
        • et al.
        The Gln-Arg 191 polymorphism of the human paraoxonase gene is not associated with the risk of coronary artery disease among Chinese in Taiwan.
        Atherosclerosis. 1998; 141: 259-264
        • Fallin D.
        • Schork N.J.
        Accuracy of haplotype frequency estimation for biallelic loci, via the expectation–maximization algorithm for unphased diploid genotype data.
        Am J Hum Genet. 2000; 67: 947-959
        • Thompson E.A.
        • Deeb S.
        • Walker D.
        • Motulsky A.G.
        The detection of linkage disequilibrium between closely linked markers: RFLPs at the AI-CIII apolipoprotein genes.
        Am J Hum Genet. 1988; 42: 113-124
        • Talmud P.J.
        • Hawe E.
        • Martin S.
        • et al.
        Relative contribution of variation within the APOC3/A4/A5 gene cluster in determining plasma triglycerides.
        Hum Mol Genet. 2002; 11: 3039-3046
        • Lee K.W.
        • Ayyobi A.F.
        • Frohlich J.J.
        • Hill J.S.
        APOA5 gene polymorphism modulates levels of triglyceride, HDL cholesterol and FERHDL but is not a risk factor for coronary artery disease.
        Atherosclerosis. 2004; 176: 165-172
        • Szalai C.
        • Keszei M.
        • Duba J.
        • et al.
        Polymorphism in the promoter region of the apolipoprotein A5 gene is associated with an increased susceptibility for coronary artery disease.
        Atherosclerosis. 2004; 173: 109-114
        • Bi N.
        • Yan S.K.
        • Li G.P.
        • Yin Z.N.
        • Chen B.S.
        A single nucleotide polymorphism -1131T > C in the apolipoprotein A5 gene is associated with an increased risk of coronary artery disease and alters triglyceride metabolism in Chinese.
        Mol Genet Metab. 2004; 83: 280-286
        • Lai C.Q.
        • Demissie S.
        • Cupples L.A.
        • et al.
        Influence of the APOA5 locus on plasma triglyceride, lipoprotein subclasses, and CVD risk in the Framingham Heart Study.
        J Lipid Res. 2004; 45: 2096-2105
        • Talmud P.J.
        • Martin S.
        • Taskinen M.R.
        • et al.
        APOA5 gene variants, lipoprotein particle distribution, and progression of coronary heart disease: results from the LOCAT study.
        J Lipid Res. 2004; 45: 750-756
        • Wong W.M.
        • Hawe E.
        • Li L.K.
        • et al.
        Apolipoprotein AIV gene variant S347 is associated with increased risk of coronary heart disease and lower plasma apolipoprotein AIV levels.
        Circ Res. 2003; 92: 969-975
        • Hubacek J.A.
        • Skodova Z.
        • Adamkova V.
        • Lanska V.
        • Poledne R.
        The influence of APOAV polymorphisms (T-1131 > C and S19 > W) on plasma triglyceride levels and risk of myocardial infarction.
        Clin Genet. 2004; 65: 126-130
        • Weinberg R.B.
        • Cook V.R.
        • Beckstead J.A.
        • et al.
        Structure and interfacial properties of human apolipoprotein A-V.
        J Biol Chem. 2003; 278: 34438-34444
        • Frohlich J.
        • Dobiasova M.
        Fractional esterification rate of cholesterol and ratio of triglycerides to HDL-cholesterol are powerful predictors of positive findings on coronary angiography.
        Clin Chem. 2003; 49: 1873-1880
        • Sattar N.
        • Petrie J.R.
        • Jaap A.J.
        The atherogenic lipoprotein phenotype and vascular endothelial dysfunction.
        Atherosclerosis. 1998; 138: 229-235
        • Schaap F.G.
        • Rensen P.C.
        • Voshol P.J.
        • et al.
        ApoAV reduces plasma triglycerides by inhibiting very low density lipoprotein-triglyceride (VLDL-TG) production and stimulating lipoprotein lipase-mediated VLDL-TG hydrolysis.
        J Biol Chem. 2004; 279: 27941-27947
        • Fruchart-Najib J.
        • Bauge E.
        • Niculescu L.S.
        • et al.
        Mechanism of triglyceride lowering in mice expressing human apolipoprotein A5.
        Biochem Biophys Res Commun. 2004; 319: 397-404
        • Jang Y.
        • Kim J.Y.
        • Kim O.Y.
        • et al.
        The -1131 T-->C polymorphism in the apolipoprotein A5 gene is associated with postprandial hypertriacylglycerolemia; elevated small, dense LDL concentrations; and oxidative stress in non-obese Korean men.
        Am J Clin Nutr. 2004; 80: 832-840