Predominant genotypes and alleles of the Val-9Ala polymorphisms in the mitochondrial targeting sequence leading the manganese superoxide dismutase gene associated with their superoxide dismutase activity and total antioxidant status of healthy Thai subjec

Watcharee Attatippaholkun, Kornwipa Wikainapakul, Saranatra Waikakul, Sirirat Tunsakul


Genotype distributions and allele frequencies of the Val-9Ala polymorphisms in the mitochondrial targeting sequence leading the manganese superoxide dismutase gene as well as associations with their superoxide dismutase activity and total antioxidant status of healthy Thai subjects were determined. The Val-9Ala polymorphisms in MTS-MnSOD gene of 221 healthy Thais including 135 females and 86 males were genotyped by a real-time PCR using protocol and all reagents of TaqMan Allelic Discrimination Demonstration Kit (PE Applied Biosystem, USA). The SOD activity of whole blood cells and plasma total antioxidant status (TAS) of each subject were assayed manually using protocol and all reagents of RANSOD and TAS kits (Randox Laboratories,UK) respectively.  The Val/Val, Val/Ala genotypes and the Val allele frequency were found to be predominant rather than the Ala/Ala genotype and the Ala allele frequency in healthy Thai subjects both females and males similar to those previous reports of healthy Chinese, Japanese and Korean subjects. The average values of SOD activity and TAS level in healthy Thais were 2,129.±778 U/g Hb and 1.27±0.26 mmol/L respectively. The association of each genotype with SOD activity as well as TAS levels of Thai females and males showed that  the average values of SOD activity and TAS in healthy Thais with the Val/Val and the Val/Ala genotypes were not statistically different (p>0.05) and not lower than those of the Ala/Ala genotypes.  In conclusion, the predominant genotypes were the Val/Val and the Val/Ala and they were not associated with low levels of SOD and TAS.


Bag, A.and Bag, N. 2008. Target sequence polymorphism of human manganese superoxide dismutase gene and its association with cancer risk: a review. Cancer Epidemiol Biomarkers Prev 17: 3298–3305.

Boom, R., Sol, C.J., Salimans, M.M., Jansen, C.L., Wertheim-van Dillen, P.M. and van der Noordaa, J. 1990. Rapid and simple method for purification of nucleic acids. J Clin Microbiol 28: 495–503.

Chistyakov, D.A., Savostanov, K.V., Zotova, E.V. and Nosikov, V.V. 2001. Polymorphisms in the MnSOD and EC-SOD genes and their relationship to diabetic neuropathy in type I diabetes mellitus. BMC Med Gen 2: 4–8.

Dasgupta, J., Subbaram, S., Connor, K.M., Rodriguez, A.M. and Tirosh. O. 2006. Manganese superoxide dismutase protects from TNF-a-induced apoptosis by increasing the steady-state production of H2O2. Antioxid Redox Signal 8: 1295–1305.

Elsakka, N.E., Webster, N.R. and Galley, H.F. 2007. Polymorphism in the manganese superoxide dismutase gene. Free Rad Res 41: 770–778.

Ezzikouri, S., El Feydi, A.E., Chafik, A., Afifi, R., El Kihal, L., Benazzouz, M., Hassar, M., Pineau, P. and Benjelloun, S. 2008. Genetic polymorphism in the manganese superoxide dismutase gene is associated with an increased risk for hepatocellular carcinoma in HCV-infected Moroccan patients. Mutat Res 649: 1–6.

Fujimoto, H., Taguchi, J., Imai, Y., Ayabe, S., Hashimoto, H., Kobayashi, H., Ogasawara, K., Aizawa, T., Yamakado, M., Nagai, R. and 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: 1267–1274.

Halliwell, B. 1997. Antioxidants and human disease: A general introduction. Nutr Rev., 55: 44–49.

Han, J., Colditz,G.A. and Hunter, D.J. 2007. Manganese superoxide dismutase polymorphism and risk of skin cancer (United States). Cancer Causes Control 18: 79–89.

Heid, C.A, Stevens, J., Livak, K.J. and Williams, P.M. 1996. Real time quantitive PCR, Genome Res 6: 986–994.

Hitzeroth, A., Niehaus, D.J., Koen, L., Botes, W.C., Deleuze, J.F. and Warnich, L. 2007. Association between the MnSOD Ala-9Val polymorphism and development of schizophrenia and abnormal involuntary movements in the Xhosa population. Prog Neuropsychopharmacol Biol Psychiatry 31: 664–672.

Ho, J.C., Mak, J.C., Ho, S.P., Tsang, K.W., Lam, W.K. and Chan-Yeung M. 2006. Manganese superoxide dismutase and catalase genetic polymorphisms, activity levels, and lung cancer risk in Chinese in Hong Kong. J Thorac Oncol 1: 648–653.

Huang, Y.S., Su, W.J., Huang, Y.H., Chen, C.Y., Chang, F.Y., Lin, H.C. and Lee, S.D. 2007. Genetic polymorphisms of manganese superoxide dismutase, NAD(P)H: quinine oxidoreductase, glutathione S-transferase M1 and T1, and the susceptibility to drug-induced liver injury. J Hepatol 47: 128–134.

Johnatty, S.E., Nagle, C.M., Spurdle, A.B.and Chen, X. 2007. Australian Breast Cancer Family Study, Webb PM, Chenevix-Trench G. The MnSOD Val9Ala polymorphism, dietary antioxidant intake, risk and survival in ovarian cancer (Australia). Gynecol Onco 107: 388–391.

Kakko, S., Päivänsalo, M., Koistinen, P., Kesäniemi, Y.A., Kinnula, V.L. and Savolainen, M.J. 2003. The signal sequence polymorphism of the MnSOD gene is associated with the degree of carotid atherosclerosis. Atherosclerosis 168: 147–152.

Kang, D., Lee, K.M., Park, S.K., Berndt, S.I., Peters, U., Reding, D., Chatterjee, N., Welch, R., Chanock, S., Huang, W.Y.and Hayes, R.B. 2007. Functional variant of manganese superoxide dismutase (SOD2 V16A) polymorphism is associated with prostate cancer risk in the prostate, lung, colorectal, and ovarian cancer study. Cancer Epidemiol Biomarkers Prev 16: 1581–1586.

Kannan, K. and Jain, S.K. 2000. Oxidative stress and apoptosis. Pathophysiology 7: 153–163.

Liu, L., Zheng, T., Wang, N., Wang, F. and Li, M. 2009. The manganese superoxide dismutase Val16Ala polymorphism is associated with decreased risk of diabetic nephropathy in Chinese patients with type 2 diabetes. Mol Cell Biochem 322: 87–91.

Mao, C., Qiu, L.X., Zhan, P., Xue, K. and Ding H. 2009. MnSOD Val (16) Ala polymorphism and prostate cancer susceptibility: A meta-analysis involving 8,962 subjects. J Cancer Res Clin Onco 136: 975–979.

Mikhak, B., Hunter, D.J., Spiegelman, D., Platz, E.A., Wu, K., Erdman, J.W.Jr., and Giovannucci, E. 2008. Manganese superoxide dismutase (MnSOD) gene polymorphism, interactions with carotenoid levels, and prostate cancer risk. Carcinogenesis 29: 2335–2340.

Murphy, S.J., Hughes, A.E., Patterson, C.C., Anderson, L.A., Watson, R.G., Johnston, B.T., Comber, H., McGuigan, J., Reynolds, J.V. and Murray, L.J. 2007. A population-based association study of SNPs of GSTP1, MnSOD, GPX2 and Barrett's esophagus and esophageal adenocarcinoma. Carcinogenesis 28: 1323–1328.

Osterreicher, C.H., Schultheiss, J., Wehler, M., Homann, N.,Hellerbrand, C., Künzli, B., Friess, H., Seitz, H.K.and Stickel, F. 2007. Genetic polymorphisms of manganese-superoxide dismutase and glutathione-S-transferase in chronic alcoholic pancreatitis. Mutagenesis 22: 305–310.

Pae, C.U., Kim, T.S., Patkar, A.A., Kim, J.J. and Lee, C.U. 2007. Manganese superoxide dismutase (MnSOD: Ala-9Val) gene polymorphism may not be associated with schizophrenia and tardive dyskinesia. Psychiatry Res 153: 77–81.

Polidori, M.C. 2003. Antioxidant micronutrients in the prevention of age-related diseases. J Postgrad Med 49: 229–235.

Rosenblum, J.S., Gilula, N.B. and Lerner, R.A. 1996. On signal sequence polymorphism and disease of distribution. Proc Natl Acad Sci USA 93: 4471–4473.

Shimoda-Matsubayashi, S., Matsumine, H., Kobayashi, T., Nakagawa-Hattori,Y., Shimizu, Y. and Mizuno, T. 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: 561–565.

Sutton, A., Imbert, A., Igoudjil, A., Descatoire, V., Cazanave, S., Pessayre, D. and Degoul, F. 2005. The manganese superoxide dismutase Ala16Val dimorphism modulates both mitochondrial import and mRNA stability. Pharmacogenet Genomics 15: 311–319.

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

The CIA-World Factbook-Thailand 2010. The World Factbook. Washington, DC: Central Intelligence Agency.

Ukeda, H., Maeda, S., Ishii, T.and Sawamura, M. 1997. Spectrophotometric assay for superoxide dismutase based on tetrazolium salt 3′-{1-[(phenyl-amino)-carbonyl]-3,4-tetrazolium}-bis(4-methoxy-6-nitro) benzenesulfonic acid hydrate reduction by xanthine-xanthine oxidase. Anal Biochem 251: 206–209.

Van Landeghem, G.F., Tabatabaie, P., Kucinskas, V., Saha, N. and Beckman, G. 1999. Ethnic variation in the mitochondrial targeting sequence polymorphism of MnSOD. Hum Hered 49: 190–193.

Ventriglia, M., Scassellati, C., Bonvicini, C., Squitti, R., Bevacqua, M.G., Foresti, G., Tura, G.B.and Gennarelli, M. 2006. No association between Ala9Val functional polymorphism of MnSOD gene and schizophrenia in a representative Italian sample. Neurosci Lett 410: 208–211.

Yu. T-W., and Ong, C. 1999. Lag-time measurement of antioxidant capacity using myoglobin and 2,2′-azino-bis (3-ethyl-benzthiazoline-6-sulfonic acid): rationale, application and limitation. Anal Biochem 275: 217–223.

Zejnilovic, J., Akev, N., Yilmaz, H. and Isbir, T. 2009. Association between manganese superoxide dismutase polymorphism and risk of lung cancer. Cancer Genetics Cytogenetics 189: 1–4.

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