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Polymorphic variations in manganese superoxide dismutase (MnSOD), glutathione peroxidase-1 (GPX1), and catalase (CAT) contribute to elevated plasma triglyceride levels in Chinese patients with type 2 diabetes or diabetic cardiovascular disease

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Abstract

Manganese superoxide dismutase (MnSOD), glutathione peroxidase-1 (GPX1), and catalase (CAT) provide the primary antioxidant defense system. Impaired antioxidant defense increases oxidative stress and contributes to the development of type 2 diabetes and diabetic cardiovascular disease (CVD). We preformed a case–control study in Chinese type 2 diabetes patients, to determine if the MnSOD Val16Ala (T→C), GPX1 Pro198Leu (C→T), and CAT −262C/T (C→T) functional polymorphisms contribute to the development of type 2 diabetes or diabetic CVD. Patients with type 2 diabetes (n = 168) were divided into the non-CVD group (n = 83, >10 year since diagnosis) and CVD group (n = 85, history of ischemic CVD). Genotyping was performed using PCR–restriction fragment length polymorphism (PCR–RFLP) or PCR-based direct sequencing. The genotypic distribution in the non-CVD- and CVD-group and the clinical parameters in genotypic groups were not significantly different in the three polymorphic sites, respectively. Among eight genotypic combinations, the most common TT+CC+CC genotype (59.5%) was associated with higher triglyceride levels than the TT+CT+CC genotype, the second frequent one (14.9%; 1.77 ± 0.12 vs. 1.21 ± 0.11 mmol/l, P = 0.001), and all non-TT+CC+CC genotypes (40.5%; 1.77 ± 0.12 vs. 1.43 ± 0.12 mmol/l, P = 0.048). In the CVD group, significantly elevated triglyceride levels were also observed in patients with TT+CC+CC compared to patients with TT+CT+CC (2.00 ± 0.18 vs. 1.37 ± 0.16 mmol/l, P = 0.018) or non-TT+CC+CC genotypes (2.00 ± 0.18 vs. 1.65 ± 0.19 mmol/l, P = 0.070). The common MnSOD, GPX1, and CAT TT+CC+CC genotype may contribute to hypertriglyceridemia in Chinese patients with type 2 diabetes or diabetic CVD.

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References

  1. Pettitt DJ, Saad MF, Bennett PH, Nelson RG, Knowler WC (1990) Familial predisposition to renal disease in two generations of Pima Indians with type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia 33:438–443

    Article  PubMed  CAS  Google Scholar 

  2. Ramakrishna V, Jailkhani R (2008) Oxidative stress in non-insulin-dependent diabetes mellitus (NIDDM) patients. Acta Diabetol 45:41–46

    Article  PubMed  CAS  Google Scholar 

  3. Creager MA, Luscher TF, Cosentino F, Beckman JA (2003) Diabetes and vascular disease: pathophysiology, clinical consequences, and medical therapy: Part I. Circulation 108:1527–1532

    Article  PubMed  Google Scholar 

  4. Singhania N, Puri D, Madhu SV, Sharma SB (2008) Assessment of oxidative stress and endothelial dysfunction in Asian Indians with type 2 diabetes mellitus with and without macroangiopathy. QJM 101(6):449–455

    Article  PubMed  CAS  Google Scholar 

  5. Nishikawa T, Edelstein D, Du XL, Yamagishi S, Matsumura T et al (2000) Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature 404(6779):787–790

    Article  PubMed  CAS  Google Scholar 

  6. Newsholme P, Haber EP, Hirabara SM, Rebelato EL, Procopio J et al (2007) Diabetes associated cell stress and dysfunction: role of mitochondrial and non-mitochondrial ROS production and activity. J Phys 583:9–24

    Article  CAS  Google Scholar 

  7. Zhang Y, Zhang HM, Shi Y, Lustgarten M, Li Y et al (2010) Loss of manganese superoxide dismutase leads to abnormal growth and signal transduction in mouse embryonic fibroblasts. Free Radic Biol Med 49(8):1255–1262

    Article  PubMed  CAS  Google Scholar 

  8. Sutton A, Khoury H, Prip-Buus C, Cepanec C, Pessayre D et al (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 

  9. Nakanishi S, Yamane K, Ohishi W, Nakashima R, Yoneda M et al (2008) Manganese superoxide dismutase Ala16Val polymorphism is associated with the development of type 2 diabetes in Japanese-Americans. Diabetes Res Clin Pract 81(3):381–385

    Article  PubMed  CAS  Google Scholar 

  10. Mollsten A, Marklund SL, Wessman M, Svensson M, Forsblom C et al (2007) A functional polymorphism in the manganese superoxide dismutase gene and diabetic nephropathy. Diabetes 56(1):265–269

    Article  PubMed  Google Scholar 

  11. Forgione MA, Weiss N, Heydrick S, Cap A, Klings ES, Bierl C, Eberhardt RT, Farber HW, Loscalzo J (2002) Cellular glutathione peroxidase deficiency and endothelial dysfunction. Am J Physiol Heart Circ Physiol 282:H1255–H1261

    PubMed  CAS  Google Scholar 

  12. Thu VT, Kim HK, Ha SH, Yoo JY, Park WS et al (2010) Glutathione peroxidase 1 protects mitochondria against hypoxia/reoxygenation damage in mouse hearts. Pflugers Arch 460(1):55–68

    Article  PubMed  CAS  Google Scholar 

  13. Shuvalova YA, Kaminnyi AI, Meshkov AN, Kukharchuk VV (2010) Pro198Leu polymorphism of GPx-1 gene and activity of erythrocytic glutathione peroxidase and lipid peroxidation products. Bull Exp Biol Med 149(6):743–745

    Article  PubMed  CAS  Google Scholar 

  14. Hamanishi T, Furuta H, Kato H, Doi A, Tamai M et al (2004) Functional variants in the glutathione peroxidase-1 (GPx-1) gene are associated with increased intima-media thickness of carotid arteries and risk of macrovascular diseases in Japanese type 2 diabetic patients. Diabetes 53:2455–2460

    Article  PubMed  CAS  Google Scholar 

  15. Gaetani GF, Ferraris AM, Rolfo M, Mangerini R, Arena S, Kirkman HN (1996) Predominant role of catalase in the disposal of hydrogen peroxide within human erythrocytes. Blood 87:1595–1599

    PubMed  CAS  Google Scholar 

  16. Forsberg L, Lyrenas L, de Faire U, Morgenstern R (2001) A common functional C-T substitution polymorphism in the promoter region of the human catalase gene influences transcription factor binding, reporter gene transcription and is correlated to blood catalase levels. Free Radic Biol Med 30(5):500–505

    Article  PubMed  CAS  Google Scholar 

  17. Bastaki M, Huen K, Manzanillo P, Chande N, Chen C et al (2006) Genotype-activity relationship for Mn-superoxide dismutase, glutathione peroxidase 1 and catalase in humans. Pharmacogenet Genomics 16(4):279–286

    Article  PubMed  CAS  Google Scholar 

  18. Chistiakov DA, Savost’anov KV, Turakulov RI, Titovich EV, Zilberman LI et al (2004) A new type 1 diabetes susceptibility locus containing the catalase gene (chromosome 11p13) in a Russian population. Diabetes Metab Res Rev 20:219–224

    Article  PubMed  CAS  Google Scholar 

  19. Pask R, Cooper JD, Walker NM, Nutland S, Hutchings J et al (2006) No evidence for a major effect of two common polymorphisms of the catalase gene in type 1 diabetes susceptibility. Diabetes Metab Res Rev 22(5):356–360

    Article  PubMed  CAS  Google Scholar 

  20. dos Santos KG, Canani LH, Gross JL, Tschiedel B, Souto KE, Roisenberg I (2006) The catalase −262C/T promoter polymorphism and diabetic complications in Caucasians with type 2 diabetes. Dis Markers 22:355–359

    PubMed  Google Scholar 

  21. Report of the expert committee on the diagnosis and classification of diabetes mellitus (2003) Diabetes Care 26 Suppl 1:S5–20

    Google Scholar 

  22. Nomiyama T, Tanaka Y, Piao L, Nagasaka K, Sakai K, Ogihara T, Nakajima K, Watada H, Kawamori R (2003) The polymorphism of manganese superoxide dismutase is associated with diabetic nephropathy in Japanese type 2 diabetic patients. J Hum Genet 48:138–141

    PubMed  CAS  Google Scholar 

  23. Perianayagam MC, Liangos O, Kolyada AY, Wald R, MacKinnon RW et al (2007) NADPH oxidase p22phox and catalase gene variants are associated with biomarkers of oxidative stress and adverse outcomes in acute renal failure. J Am Soc Nephrol 18(1):255–263

    Article  PubMed  CAS  Google Scholar 

  24. Lee SJ, Choi MG (2006) Association of manganese superoxide dismutase gene polymorphism (V16A) with stages of albuminuria in Korean type 2 diabetic patients. Metabolism 55:1681–1688

    Article  PubMed  CAS  Google Scholar 

  25. Kangas-Kontio T, Vavuli S, Kakko SJ, Penna J, Savolainen ER et al (2009) Polymorphism of the manganese superoxide dismutase gene but not of vascular endothelial growth factor gene is a risk factor for diabetic retinopathy. Br J Ophthalmol 93:1401–1406

    Article  PubMed  CAS  Google Scholar 

  26. Nemoto M, Nishimura R, Sasaki T, Hiki Y, Miyashita Y et al (2007) Genetic association of glutathione peroxidase-1 with coronary artery calcification in type 2 diabetes: a case control study with multi-slice computed tomography. Cardiovasc Diabetol 6:23

    Article  PubMed  Google Scholar 

  27. Sniderman AD, Scantlebury T, Cianflone K (2001) Hypertriglyceridemic hyperapob: the unappreciated atherogenic dyslipoproteinemia in type 2 diabetes mellitus. Ann Intern Med 135:447–459

    PubMed  CAS  Google Scholar 

  28. Cummings MH, Watts GF, Umpleby AM, Hennessy TR, Naoumova R et al (1995) Increased hepatic secretion of very-low-density lipoprotein apolipoprotein B-100 in NIDDM. Diabetologia 38:959–967

    Article  PubMed  CAS  Google Scholar 

  29. Aviram M (2009) Hyperlipidaemia and cardiovascular disease: inflammation and oxidative stress in diabetic patients. Curr Opin Lipidol 20(3):258–259

    Article  PubMed  CAS  Google Scholar 

  30. He S, Wang S, Chen X, Jiang L, Peng Y, Li L, Wan L, Cui K (2011) Higher ratio of triglyceride to high-density lipoprotein cholesterol may predispose to diabetes mellitus: 15-year prospective study in a general population. Metabolism. doi:10.1016/i.metabol.2011.05.007

  31. Nishikawa T, Sasahara T, Kiritoshi S, Sonoda K, Senokuchi T et al (2003) Evaluation of urinary 8-hydroxydeoxy-guanosine as a novel biomarker of macrovascular complications in type 2 diabetes. Diabetes Care 26(5):1507–1512

    Article  PubMed  CAS  Google Scholar 

  32. Fujita A, Sasaki H, Ogawa K, Okamoto K, Matsuno S et al (2005) Increased gene expression of antioxidant enzymes in KKAy diabetic mice but not in STZ diabetic mice. Diabetes Res Clin Pract 69(2):113–119

    Article  PubMed  CAS  Google Scholar 

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Acknowledgment

This research was supported by Grant (30971384) from the Project of National Nature Science Foundation of China and by Grant (10XD1403400) from the Shanghai Scientific & Technical Committee Foundation.

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Correspondence to Limei Liu.

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Hong Chen and Ming Yu contributed equally to this study.

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Chen, H., Yu, M., Li, M. et al. Polymorphic variations in manganese superoxide dismutase (MnSOD), glutathione peroxidase-1 (GPX1), and catalase (CAT) contribute to elevated plasma triglyceride levels in Chinese patients with type 2 diabetes or diabetic cardiovascular disease. Mol Cell Biochem 363, 85–91 (2012). https://doi.org/10.1007/s11010-011-1160-3

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  • DOI: https://doi.org/10.1007/s11010-011-1160-3

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