Plasma extracellular superoxide dismutase concentration, allelic variations in the SOD3 gene and risk of myocardial infarction and all-cause mortality in people with type 1 and type 2 diabetes

Cardiovascular Diabetology

Gilberto Velho⁸  Michel Marre⁵  Samy Hadjadj²  Ronan Roussel⁵  Frédéric Fumeron⁵  Thiago A Patente⁶  Hervé Le Nagard⁷  Fathi Driss¹  Stefan L Marklund⁴  Naïma Bellili-Muñoz⁸  Kamel Mohammedi³ 

[1] Assistance Publique Hôpitaux de Paris, Department of Biochemistry, Bichat Hospital, 46 rue Henri Huchard, Paris, 75018, France;Department of Endocrinology and Diabetology, Centre Hospitalier Universitaire de Poitiers, 2 Rue de la Milétrie, Poitiers, 86021, France;Assistance Publique Hôpitaux de Paris, DHU FIRE, Department of Diabetology, Endocrinology and Nutrition, Bichat Hospital, 46 rue Henri Huchard, Paris, 75018, France;Department of Medical Biosciences, Umeå University, Building 6M, Umeå, 90185, Sweden;Sorbonne Paris Cité, UFR de Médecine, Université Paris Diderot, 16 rue Henri Huchard, Paris, 75018, France;Laboratório de Endocrinologia Celular e Molecular (LIM-25), Faculdade de Medicina da Universidade de São Paulo (FMUSP), Avenida Dr. Arnaldo 455, São Paulo, CEP 01246903, SP, Brazil;INSERM, Research Unit 1137 - IAME, 16 rue Henri Huchard, Paris, 75018, France;INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, 15 rue de l’École de Médecine, Paris, 75006, France

关键词: Diabetes Mellitus;    Mortality;    Myocardial Infarction;    SOD3;    Oxidative Stress;   

Others  :  1123414
DOI  :  10.1186/s12933-014-0163-2

 received in 2014-09-11, accepted in 2014-12-10,  发布年份 2015

【 摘 要 】

Background

Oxidative stress is involved in development of diabetes complications. Extracellular superoxide dismutase (EC-SOD, SOD3) is a major extracellular antioxidant enzyme and is highly expressed in arterial walls. Advanced oxidation protein products (AOPP) and 8-iso-prostaglandin (isoprostane) are markers of oxidative stress. We investigated association of SOD3 gene variants, plasma concentrations of EC-SOD, AOPP and isoprostane with myocardial infarction and mortality in diabetic patients.

Methods

We studied three cohorts designed to evaluate the vascular complications of diabetes: the GENEDIAB study (469 participants with type 1 diabetes at baseline; follow-up data for 259 participants), the GENESIS study (603 participants with type 1 diabetes at baseline; follow-up data for 525 participants) and the DIABHYCAR study (3137 participants with type 2 diabetes at baseline and follow-up). Duration of follow-up was 9, 5, and 5 years, respectively. Main outcome measures were incidence of myocardial infarction, and cardiovascular and total mortality during follow-up. Six single nucleotide polymorphisms in the SOD3 locus were genotyped in the three cohorts. Plasma concentrations of EC-SOD, AOPP, and isoprostane were measured in baseline samples of GENEDIAB participants.

Results

In GENEDIAB/GENESIS pooled cohorts, the minor T-allele of rs2284659 variant was inversely associated with the prevalence at baseline (Odds Ratio 0.48, 95% CI 0.29–0.78, p = 0.004) and the incidence during follow-up of myocardial infarction (Hazard Ratio 0.58, 95% CI 0.40–0.83, p = 0.003) and with cardiovascular (HR 0.33, 95% CI 0.08–0.74, p = 0.004) and all-cause mortality (HR 0.44, 95% CI 0.21–0.73, p = 0.0006). The protective allele was associated with higher plasma EC-SOD and lower plasma AOPP concentrations in GENEDIAB. It was also inversely associated with incidence of myocardial infarction (HR 0.75, 95% CI 0.59–0.94, p = 0.01) and all-cause mortality (HR 0.87, 95% CI 0.79–0.97, p = 0.008) in DIABHYCAR.

Conclusions

The T-allele of rs2284659 in the promoter of SOD3 was associated with a more favorable plasma redox status and with better cardiovascular outcomes in diabetic patients. Our results suggest that EC-SOD plays an important role in the mechanisms of vascular protection against diabetes-related oxidative stress.

【 授权许可】

   
2015 Mohammedi et al.; licensee BioMed Central.

【 参考文献 】

• [1]Soedamah-Muthu SS, Fuller JH, Mulnier HE, Raleigh VS, Lawrenson RA, Colhoun HM: All-cause mortality rates in patients with type 1 diabetes mellitus compared with a non-diabetic population from the UK general practice research database, 1992–1999. Diabetologia 2006, 49(4):660-666.
• [2]Seshasai SR, Kaptoge S, Thompson A, Di Angelantonio E, Gao P, Sarwar N, Whincup PH, Mukamal KJ, Gillum RF, Holme I, Njolstad I, Fletcher A, Nilsson P, Lewington S, Collins R, Gudnason V, Thompson SG, Sattar N, Selvin E, Hu FB, Danesh J: Diabetes mellitus, fasting glucose, and risk of cause-specific death.N Engl J Med 2011, 364(9):829-841.
• [3]Almdal T, Scharling H, Jensen JS, Vestergaard H: The independent effect of type 2 diabetes mellitus on ischemic heart disease, stroke, and death: a population-based study of 13,000 men and women with 20 years of follow-up. Arch Intern Med 2004, 164(13):1422-1426.
• [4]Pfister R, Barnes D, Luben RN, Khaw KT, Wareham NJ, Langenberg C: Individual and cumulative effect of type 2 diabetes genetic susceptibility variants on risk of coronary heart disease. Diabetologia 2011, 54(9):2283-2287.
• [5]Giacco F, Brownlee M: Oxidative stress and diabetic complications. Circ Res 2010, 107(9):1058-1070.
• [6]Fridovich I: Superoxide radical and superoxide dismutases. Annu Rev Biochem 1995, 64:97-112.
• [7]Stralin P, Karlsson K, Johansson BO, Marklund SL: The interstitium of the human arterial wall contains very large amounts of extracellular superoxide dismutase. Arterioscler Thromb Vasc Biol 1995, 15(11):2032-2036.
• [8]Landmesser U, Merten R, Spiekermann S, Buttner K, Drexler H, Hornig B: Vascular extracellular superoxide dismutase activity in patients with coronary artery disease: relation to endothelium-dependent vasodilation. Circulation 2000, 101(19):2264-2270.
• [9]Takatsu H, Tasaki H, Kim HN, Ueda S, Tsutsui M, Yamashita K, Toyokawa T, Morimoto Y, Nakashima Y, Adachi T: Overexpression of EC-SOD suppresses endothelial-cell-mediated LDL oxidation. Biochem Biophys Res Commun 2001, 285(1):84-91.
• [10]Kaneda H, Taguchi J, Ogasawara K, Aizawa T, Ohno M: Increased level of advanced oxidation protein products in patients with coronary artery disease. Atherosclerosis 2002, 162(1):221-225.
• [11]LeLeiko RM, Vaccari CS, Sola S, Merchant N, Nagamia SH, Thoenes M, Khan BV: Usefulness of elevations in serum choline and free F2)-isoprostane to predict 30-day cardiovascular outcomes in patients with acute coronary syndrome. Am J Cardiol 2009, 104(5):638-643.
• [12]Marre M, Jeunemaitre X, Gallois Y, Rodier M, Chatellier G, Sert C, Dusselier L, Kahal Z, Chaillous L, Halimi S, Muller A, Sackmann H, Bauduceau B, Bled F, Passa P, Alhenc-Gelas F: Contribution of genetic polymorphism in the renin-angiotensin system to the development of renal complications in insulin-dependent diabetes: Genetique de la Nephropathie Diabetique (GENEDIAB) study group.J Clin Invest 1997, 99(7):1585-1595.
• [13]Hadjadj S, Pean F, Gallois Y, Passa P, Aubert R, Weekers L, Rigalleau V, Bauduceau B, Bekherraz A, Roussel R, Dussol B, Rodier M, Marechaud R, Lefebvre PJ, Marre M: Different patterns of insulin resistance in relatives of type 1 diabetic patients with retinopathy or nephropathy: the Genesis France-Belgium Study.Diabetes Care 2004, 27(11):2661-2668.
• [14]Marre M, Lievre M, Chatellier G, Mann JF, Passa P, Menard J: Effects of low dose ramipril on cardiovascular and renal outcomes in patients with type 2 diabetes and raised excretion of urinary albumin: randomised, double blind, placebo controlled trial (the DIABHYCAR study). BMJ 2004, 328(7438):495.
• [15]Karlsson K, Marklund SL: Plasma clearance of human extracellular-superoxide dismutase C in rabbits. J Clin Invest 1988, 82(3):762-766.
• [16]Witko-Sarsat V, Friedlander M, Capeillere-Blandin C, Nguyen-Khoa T, Nguyen AT, Zingraff J, Jungers P, Descamps-Latscha B: Advanced oxidation protein products as a novel marker of oxidative stress in uremia. Kidney Int 1996, 49(5):1304-1313.
• [17]Sandstrom J, Nilsson P, Karlsson K, Marklund SL: 10-fold increase in human plasma extracellular superoxide dismutase content caused by a mutation in heparin-binding domain. J Biol Chem 1994, 269(29):19163-19166.
• [18]Nyholt DR: A simple correction for multiple testing for single-nucleotide polymorphisms in linkage disequilibrium with each other. Am J Hum Genet 2004, 74(4):765-769.
• [19]Descamps-Latscha B, Witko-Sarsat V, Nguyen-Khoa T, Nguyen AT, Gausson V, Mothu N, London GM, Jungers P: Advanced oxidation protein products as risk factors for atherosclerotic cardiovascular events in nondiabetic predialysis patients. Am J Kidney Dis 2005, 45(1):39-47.
• [20]Feng Y, Shen C, Ma G, Wang J, Chen Z, Dai Q, Zhi H, Yang C, Fu Q, Shang G, Guan Y: Prolonged pain to hospital time is associated with increased plasma advanced oxidation protein products and poor prognosis in patients with percutaneous coronary intervention for ST-elevation myocardial infarction.Heart Vessels 2010, 25(5):374-378.
• [21]Neves AL, Mohammedi K, Emery N, Roussel R, Fumeron F, Marre M, Velho G: Allelic variations in superoxide dismutase-1 (SOD1) gene and renal and cardiovascular morbidity and mortality in type 2 diabetic subjects. Mol Genet Metab 2012, 106:359-365.
• [22]Mollsten A, Jorsal A, Lajer M, Vionnet N, Tarnow L: The V16A polymorphism in SOD2 is associated with increased risk of diabetic nephropathy and cardiovascular disease in type 1 diabetes. Diabetologia 2009, 52:2590-2593.
• [23]Adachi T, Yamada H, Yamada Y, Morihara N, Yamazaki N, Murakami T, Futenma A, Kato K, Hirano K: Substitution of glycine for arginine-213 in extracellular-superoxide dismutase impairs affinity for heparin and endothelial cell surface. Biochem J 1996, 313(Pt 1):235-239.
• [24]Chu Y, Alwahdani A, Iida S, Lund DD, Faraci FM, Heistad DD: Vascular effects of the human extracellular superoxide dismutase R213G variant. Circulation 2005, 112(7):1047-1053.
• [25]Marklund SL, Nilsson P, Israelsson K, Schampi I, Peltonen M, Asplund K: Two variants of extracellular-superoxide dismutase: relationship to cardiovascular risk factors in an unselected middle-aged population. J Intern Med 1997, 242(1):5-14.
• [26]Juul K, Tybjaerg-Hansen A, Marklund S, Heegaard NH, Steffensen R, Sillesen H, Jensen G, Nordestgaard BG: Genetically reduced antioxidative protection and increased ischemic heart disease risk: the Copenhagen City heart study. Circulation 2004, 109(1):59-65.
• [27]Chang CP, Stankunas K, Shang C, Kao SC, Twu KY, Cleary ML: Pbx1 functions in distinct regulatory networks to pattern the great arteries and cardiac outflow tract. Development 2008, 135(21):3577-3586.
• [28]Arrington CB, Dowse BR, Bleyl SB, Bowles NE: Non-synonymous variants in pre-B cell leukemia homeobox (PBX) genes are associated with congenital heart defects. Eur J Med Genet 2012, 55(4):235-237.
• [29]Weng YJ, Hsieh DJ, Kuo WW, Lai TY, Hsu HH, Tsai CH, Tsai FJ, Lin DY, Lin JA, Huang CY, Tung KC: E4BP4 is a cardiac survival factor and essential for embryonic heart development.Mol Cell Biochem 2010, 340(1-2):187-194.
• [30]Libby P, Ridker PM, Hansson GK: Progress and challenges in translating the biology of atherosclerosis. Nature 2011, 473(7347):317-325.
• [31]Higashi Y, Noma K, Yoshizumi M, Kihara Y: Endothelial function and oxidative stress in cardiovascular diseases. Circ J 2009, 73(3):411-418.
• [32]Patel H, Chen J, Das KC, Kavdia M: Hyperglycemia induces differential change in oxidative stress at gene expression and functional levels in HUVEC and HMVEC. Cardiovasc Diabetol 2013, 12:142. BioMed Central Full Text
• [33]Faraci FM, Didion SP: Vascular protection: superoxide dismutase isoforms in the vessel wall. Arterioscler Thromb Vasc Biol 2004, 24(8):1367-1373.
• [34]Rosa CM, Xavier NP, Henrique Campos D, Fernandes AA, Cezar MD, Martinez PF, Cicogna AC, Gimenes C, Gimenes R, Okoshi MP, Okoshi K: Diabetes mellitus activates fetal gene program and intensifies cardiac remodeling and oxidative stress in aged spontaneously hypertensive rats.Cardiovasc Diabetol 2013, 12(1):152
• [35]Hopps E, Noto D, Caimi G, Averna MR: A novel component of the metabolic syndrome: the oxidative stress. Nutr Metab Cardiovasc Dis 2010, 20(1):72-77.
• [36]Heslop CL, Frohlich JJ, Hill JS: Myeloperoxidase and C-reactive protein have combined utility for long-term prediction of cardiovascular mortality after coronary angiography. J Am Coll Cardiol 2010, 55(11):1102-1109.
• [37]Doney AS, Lee S, Leese GP, Morris AD, Palmer CN: Increased cardiovascular morbidity and mortality in type 2 diabetes is associated with the glutathione S transferase theta-null genotype: a Go-DARTS study. Circulation 2005, 111(22):2927-2934.
• [38]Stull LB, Leppo MK, Szweda L, Gao WD, Marban E: Chronic treatment with allopurinol boosts survival and cardiac contractility in murine postischemic cardiomyopathy. Circ Res 2004, 95(10):1005-1011.
• [39]Zhang S, Liu H, Amarsingh GV, Cheung CC, Hogl S, Narayanan U, Zhang L, McHarg S, Xu J, Gong D, Kennedy J, Barry B, Choong YS, Phillips AR, Cooper GJ: Diabetic cardiomyopathy is associated with defective myocellular copper regulation and both defects are rectified by divalent copper chelation.Cardiovasc Diabetol 2014, 13:100.
• [40]Oury TD, Day BJ, Crapo JD: Extracellular superoxide dismutase in vessels and airways of humans and baboons. Free Radic Biol Med 1996, 20(7):957-965.
• [41]Chen EP, Bittner HB, Davis RD, Folz RJ, Van Trigt P: Extracellular superoxide dismutase transgene overexpression preserves postischemic myocardial function in isolated murine hearts. Circulation 1996, 94(9 Suppl):II412-417.
• [42]Li Q, Bolli R, Qiu Y, Tang XL, Guo Y, French BA: Gene therapy with extracellular superoxide dismutase protects conscious rabbits against myocardial infarction. Circulation 2001, 103(14):1893-1898.
• [43]Sentman ML, Brannstrom T, Westerlund S, Laukkanen MO, Yla-Herttuala S, Basu S, Marklund SL: Extracellular superoxide dismutase deficiency and atherosclerosis in mice. Arterioscler Thromb Vasc Biol 2001, 21(9):1477-1482.
• [44]Sheng H, Brady TC, Pearlstein RD, Crapo JD, Warner DS: Extracellular superoxide dismutase deficiency worsens outcome from focal cerebral ischemia in the mouse. Neurosci Lett 1999, 267(1):13-16.
• [45]Sheng H, Bart RD, Oury TD, Pearlstein RD, Crapo JD, Warner DS: Mice overexpressing extracellular superoxide dismutase have increased resistance to focal cerebral ischemia. Neuroscience 1999, 88(1):185-191.