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Association of C47T polymorphism in SOD2 gene with coronary artery disease: a case–control study and a meta-analysis

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Abstract

Oxidative damage promotes atherosclerosis. SOD2 is an important antioxidant enzyme. A case–control study and a meta-analysis were performed to assess the association of C47T polymorphism in SOD2 gene with premature, late-onset and overall coronary artery disease (CAD) risk. A hospital-based case–control study was conducted with 269 premature CAD cases, 278 late-onset CAD cases and 299 healthy controls. Polymerase chain reaction (PCR) and Pyrosequencing were used to detect the polymorphism. Multinomial logistic regression model was performed to estimate odds ratio (OR) with 95% confidence intervals (CIs) and adjust potential confounders. A meta-analysis was performed using eight outcomes including our result. Fixed or random effect pooled measure was selected on the basis of homogeneity test among studies. Heterogeneity among studies was evaluated using I 2. Meta-regression was used to explore potential sources of between-study heterogeneity. Publication bias was estimated using Peters’s linear regression test. In our case–control study, compared with the TT as the reference, the mutant genotype of CC + TC was significantly associated with a reduced premature CAD risk both in univariate (OR = 0.60, 95% CI = 0.41–0.87) and multivariate (OR = 0.59, 95% CI = 0.40–0.87) logistic regressions, but not with late-onset CAD risk. After excluding one article that deviated from Hardy–Weinberg equilibrium in controls, this meta-analysis showed a significant association of the C allele with reduced risk of CAD in dominant (FEM: OR = 0.69, 95% CI = 0.61–0.78), recessive (OR = 0.64, 95% CI = 0.50–0.82), and codominant (FEM: OR = 0.73, 95% CI = 0.65–0.80) models. Our study suggested that the mutant genotype of CC + TC was significantly associated with a reduced CAD risk.

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References

  1. Singh U, Jialal I (2006) Oxidative stress and atherosclerosis. Pathophysiology 13(3):129–142

    Article  PubMed  CAS  Google Scholar 

  2. Oberley TD, Oberley LW (1997) Antioxidant enzyme levels in cancer. Histol Histopathol 12(2):525–535

    PubMed  CAS  Google Scholar 

  3. Shimoda-Matsubayashi S, Matsumine H, Kobayashi T, Nakagawa-Hattori Y, Shimizu Y, Mizuno Y (1996) Structural dimorphism in the mitochondrial targeting sequence in the human manganese superoxide dismutase gene. A predictive evidence for conformational change to influence mitochondrial transport and a study of allelic association in Parkinson’s disease. Biochem Biophys Res Commun 226(2):561–565

    Article  PubMed  CAS  Google Scholar 

  4. Fang X, Weintraub NL, Rios CD, Chappell DA, Zwacka RM, Engelhardt JF, Oberley LW, Yan T, Heistad DD, Spector AA (1998) Overexpression of human superoxide dismutase inhibits oxidation of low-density lipoprotein by endothelial cells. Circ Res 82(12):1289–1297

    PubMed  CAS  Google Scholar 

  5. Kinscherf R, Claus R, Wagner M, Gehrke C, Kamencic H, Hou D, Nauen O, Schmiedt W, Kovacs G, Pill J, Metz J, Deigner HP (1998) Apoptosis caused by oxidized LDL is manganese superoxide dismutase and p53 dependent. FASEB J 12(6):461–467

    PubMed  CAS  Google Scholar 

  6. Ohashi M, Runge MS, Faraci FM, Heistad DD (2006) MnSOD deficiency increases endothelial dysfunction in ApoE-deficient mice. Arterioscler Thromb Vasc Biol 26(10):2331–2336

    Article  PubMed  CAS  Google Scholar 

  7. Sutton A, Khoury H, Prip-Buus C, Cepanec C, Pessayre D, Degoul F (2003) The Ala16Val genetic dimorphism modulates the import of human manganese superoxide dismutase into rat liver mitochondria. Pharmacogenetics 13(3):145–157

    Article  PubMed  CAS  Google Scholar 

  8. Fujimoto H, Taguchi J, Imai Y, Ayabe S, Hashimoto H, Kobayashi H, Ogasawara K, Aizawa T, Yamakado M, Nagai R, Ohno M (2008) Manganese superoxide dismutase polymorphism affects the oxidized low-density lipoprotein-induced apoptosis of macrophages and coronary artery disease. Eur Heart J 29(10):1267–1274

    Article  PubMed  CAS  Google Scholar 

  9. Chaer RA, Billeh R, Massad MG (2004) Genetics and gene manipulation therapy of premature coronary artery disease. Cardiology 101(1–3):122–130

    Article  PubMed  Google Scholar 

  10. Members of the focus group for dyslipidemia prevention and control (1997) Suggestions for dyslipidemia prevention and control. Zhonghua Xin Xue Guan Bing Za Zhi 25(3):169–172

    Google Scholar 

  11. Report of the Joint International Society and Fed eration of Cardiology/World Health Organization task force on standardization of clinical nomenclature (1979) Nomenclature and criteria for diagnosis of ischemic heart disease. Circulation 59(3):607–609

    Google Scholar 

  12. Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21(11):1539–1558

    Article  PubMed  Google Scholar 

  13. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. Br Med J 327(7414):557–560

    Article  Google Scholar 

  14. Patsopoulos NA, Evangelou E, Ioannidis JP (2008) Sensitivity of between-study heterogeneity in meta-analysis: proposed metrics and empirical evaluation. Int J Epidemiol 37(5):1148–1157

    Article  PubMed  Google Scholar 

  15. Peters JL, Sutton AJ, Jones DR, Abrams KR, Rushton L (2006) Comparison of two methods to detect publication bias in meta-analysis. JAMA 295(6):676–680

    Article  PubMed  CAS  Google Scholar 

  16. Tobias A (1999) Assessing the influence of a single study in the meta-analysis estimate. Stata Tech Bull 47:15–17

    Google Scholar 

  17. Chi DS, Ling WH, Ma J, Xia M, Hou MJ, Wang Q, Zhu HL, Tang ZH, Xu X (2006) Association between manganese superoxide dismutase 9Ala/Val genetic polymorphism and coronary artery dismutase. Zhongguo Gong Gong Wei Sheng 22(9):1078–1080

    CAS  Google Scholar 

  18. Fujimoto H, Kobayashi H, Ogasawara K, Yamakado M, Ohno M (2010) Association of the manganese superoxide dismutase polymorphism with vasospastic angina pectoris. J Cardiol 55(2):205–210

    Article  PubMed  Google Scholar 

  19. Katakami N, Kaneto H, Matsuoka TA, Takahara M, Imamura K, Ishibashi F, Kanda T, Kawai K, Osonoi T, Kashiwagi A, Kawamori R, Matsuhisa M, Shimomura I, Yamasaki Y (2010) Accumulation of gene polymorphisms related to oxidative stress is associated with myocardial infarction in Japanese type 2 diabetic patients. Atherosclerosis 212(2):534–538

    Article  PubMed  CAS  Google Scholar 

  20. Mollsten A, Jorsal A, Lajer M, Vionnet N, Tarnow L (2009) The V16A polymorphism in SOD2 is associated with increased risk of diabetic nephropathy and cardiovascular disease in type 1 diabetes. Diabetologia 52(12):2590–2593

    Article  PubMed  CAS  Google Scholar 

  21. Yang MP, Ye LX, Qiu H, Deng MD, Wang Q, Li QL, Lei T, Chi D (2008) Association between manganese superoxide dismutase 9Ala/Val genetic polymorphisms and coronary heart disease. Wu Han Da Xue Xue Bao 29(6):775–779

    CAS  Google Scholar 

  22. Jones DA, Prior SL, Tang TS, Bain SC, Hurel SJ, Humphries SE, Stephens JW (2010) Association between the rs4880 superoxide dismutase 2 (C>T) gene variant and coronary heart disease in diabetes mellitus. Diabetes Res Clin Pract 90(2):196–201

    Article  PubMed  CAS  Google Scholar 

  23. Vaidya D, Yanek LR, Moy TF, Pearson TA, Becker LC, Becker DM (2007) Incidence of coronary artery disease in siblings of patients with premature coronary artery disease: 10 years of follow-up. Am J Cardiol 100(9):1410–1415

    Article  PubMed  Google Scholar 

  24. Shah SH, Freedman NJ, Zhang L, Crosslin DR, Stone DH, Haynes C, Johnson J, Nelson S, Wang L, Connelly JJ, Muehlbauer M, Ginsburg GS, Crossman DC, Jones CJ, Vance J, Sketch MH, Granger CB, Newgard CB, Gregory SG, Goldschmidt-Clermont PJ, Kraus WE, Hauser ER (2009) Neuropeptide Y gene polymorphisms confer risk of early-onset atherosclerosis. PLoS Genet 5(1):e1000318

    Article  PubMed  Google Scholar 

  25. Mani A, Radhakrishnan J, Wang H, Mani MA, Nelson-Williams C, Carew KS, Mane S, Najmabadi H, Wu D, Lifton RP (2007) LRP6 mutation in a family with early coronary disease and metabolic risk factors. Science 315(5816):1278–1282

    Article  PubMed  CAS  Google Scholar 

  26. Samani NJ, Burton P, Mangino M, Ball SG, Balmforth AJ, Barrett J, Bishop T, Hall A (2005) A genomewide linkage study of 1,933 families affected by premature coronary artery disease: the British Heart Foundation (BHF) Family Heart Study. Am J Hum Genet 77(6):1011–1020

    Article  PubMed  Google Scholar 

  27. Wang Q, Rao S, Shen GQ, Li L, Moliterno DJ, Newby LK, Rogers WJ, Cannata R, Zirzow E, Elston RC, Topol EJ (2004) Premature myocardial infarction novel susceptibility locus on chromosome 1P34–36 identified by genomewide linkage analysis. Am J Hum Genet 74(2):262–271

    Article  PubMed  CAS  Google Scholar 

  28. Zdravkovic S, Wienke A, Pedersen NL, Marenberg ME, Yashin AI, De Faire U (2002) Heritability of death from coronary heart disease: a 36-year follow-up of 20 966 Swedish twins. J Intern Med 252(3):247–254

    Article  PubMed  CAS  Google Scholar 

  29. Marenberg ME, Risch N, Berkman LF, Floderus B, de Faire U (1994) Genetic susceptibility to death from coronary heart disease in a study of twins. N Engl J Med 330(15):1041–1046

    Article  PubMed  CAS  Google Scholar 

  30. Munafo MR, Flint J (2004) Meta-analysis of genetic association studies. Trends Genet 20(9):439–444

    Article  PubMed  CAS  Google Scholar 

  31. Sterne JA, Gavaghan D, Egger M (2000) Publication and related bias in meta-analysis: power of statistical tests and prevalence in the literature. J Clin Epidemiol 53(11):1119–1129

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This study was sponsored by a grant from Shandong Provincial Natural Science Foundation, China (Y2007C005).

Conflict of interest

The authors declare that there are no conflicts of interest.

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Authors and Affiliations

  1. Department of Epidemiology and Health Statistics, Shandong University, Jinan, 250012, Shandong, People’s Republic of China

    Changwei Tian, Shengxia Fang, Xunbo Du & Chongqi Jia

  2. Department of Cardiology, Qilu Hospital, Shandong University, Jinan, 250012, Shandong, People’s Republic of China

    Tongtao Liu

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  1. Changwei Tian
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  2. Tongtao Liu
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  3. Shengxia Fang
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Correspondence to Chongqi Jia.

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Changwei Tian and Tongtao Liu equally share the first authorship.

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Tian, C., Liu, T., Fang, S. et al. Association of C47T polymorphism in SOD2 gene with coronary artery disease: a case–control study and a meta-analysis. Mol Biol Rep 39, 5269–5276 (2012). https://doi.org/10.1007/s11033-011-1324-y

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  • DOI: https://doi.org/10.1007/s11033-011-1324-y

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