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Common polymorphisms in antioxidant genes are associated with diabetic nephropathy in Type 2 diabetes patients

    Jasna Klen

    General Hospital Trbovlje, Rudarska cesta 9, 1420 Trbovlje, Slovenia

    ,
    Katja Goričar

    Pharmacogenetics Laboratory, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia

    ,
    Andrej Janež

    Department of Endocrinology, Diabetes & Metabolic Diseases, University Medical Center Ljubljana, Zaloška cesta 7, 1000 Ljubljana, Slovenia

    &
    Vita Dolžan

    *Author for correspondence:

    E-mail Address: vita.dolzan@mf.uni-lj.si

    Pharmacogenetics Laboratory, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia

    Published Online:https://doi.org/10.2217/pme.14.86

    Aim: To investigate if antioxidative genes’ polymorphisms influence the risk for Type 2 diabetes (T2D) complications. Materials & Methods: In total, 181 T2D patients were genotyped for SOD2, CAT, GPX1, GSTP1, GSTM1*0, GSTT1*0, GCLC and GCLM.Results: After adjustment for duration of T2D, CAT rs1001179 and GSTP1 rs1138272 showed strongest association with risk for end-stage kidney failure (p = 0.005 and p = 0.049, respectively). In patients without end-stage kidney failure CAT rs1001179 influenced urea levels (p = 0.003), while GSTP1 rs1695 and GSTP1 haplotypes influenced the risk of moderately increased albuminuria (p = 0.024 and p = 0.014, respectively). Conclusion: Common CAT and GSTP1 polymorphisms could be used to identify T2D patients at an increased risk for developing end-stage kidney failure.

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

    References

    • 1 Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with Type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet 352(9131), 837–853 (1998).
    • 2 Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10 year follow-up of intensive glucose control in Type 2 diabetes. N. Engl. J. Med. 359(15), 1577–1589 (2008).
    • 3 Park J, Lertdumrongluk P, Molnar MZ, Kovesdy CP, Kalantar-Zadeh K. Glycemic control in diabetic dialysis patients and the burnt-out diabetes phenomenon. Curr. Diab. Rep. 12(4), 432–439 (2012).
    • 4 Ritz E. Clinical manifestations and natural history of diabetic kidney disease. Med. Clin. North Am. 97(1), 19–29 (2013).
    • 5 Coca SG, Ismail-Beigi F, Haq N, Krumholz HM, Parikh CR. Role of intensive glucose control in development of renal end points in Type 2 diabetes mellitus: systematic review and meta-analysis intensive glucose control in Type 2 diabetes. Arch. Intern. Med. 172(10), 761–769 (2012).
    • 6 Badal SS, Danesh FR. New insights into molecular mechanisms of diabetic kidney disease. Am. J. Kidney Dis. 63(2 Suppl. 2), s63–s83 (2014).
    • 7 Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature 414(6865), 813–820 (2001).
    • 8 Sasaki S, Inoguchi T. The role of oxidative stress in the pathogenesis of diabetic vascular complications. Diab. Metab. J. 36(4), 255–261 (2012).
    • 9 Mohanty P, Hamouda W, Garg R, Aljada A, Ghanim H, Dandona P. Glucose challenge stimulates reactive oxygen species (ROS) generation by leucocytes. J. Clin. Endocrinol. Metab. 85(8), 2970–2973 (2000).
    • 10 Satirapoj B. Nephropathy in diabetes. Adv. Exp. Med. Biol. 771, 107–122 (2012).
    • 11 Stanton RC. Oxidative stress and diabetic kidney disease. Curr. Diab. Rep. 11(4), 330–336 (2011).
    • 12 Sun YM, Su Y, Li J, Wang LF. Recent advances in understanding the biochemical and molecular mechanism of diabetic nephropathy. Biochem. Biophys. Res. Commun. 433(4), 359–361 (2013).
    • 13 Crawford A, Fassett RG, Geraghty DP et al. Relationships between single nucleotide polymorphisms of antioxidant enzymes and disease. Gene 501(2), 89–103 (2012).
    • 14 Forsberg L, De Faire U, Morgenstern R. Oxidative stress, human genetic variation, and disease. Arch. Biochem. Biophys. 389(1), 84–93 (2001).
    • 15 Tang ST, Wang CJ, Tang HQ, Zhang Q, Wang Y. Evaluation of glutathione-S-transferase genetic variants affecting Type 2 diabetes susceptibility: a meta-analysis. Gene 530(2), 301–308 (2013).
    • 16 Zhang J, Liu H, Yan H, Huang G, Wang B. Null genotypes of GSTM1 and GSTT1 contribute to increased risk of diabetes mellitus: a meta-analysis. Gene 518(2), 405–411 (2013).
    • 17 Johansen JS, Harris AK, Rychly DJ, Ergul A. Oxidative stress and the use of antioxidants in diabetes: linking basic science to clinical practice. Cardiovasc. Diabetol. 4(1), 5 (2005).
    • 18 American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 35 (Suppl. 1), s64–s71 (2012) .
    • 19 WHO/IDF. Definition and diagnosis of diabetes mellitus and intermediate hyperglycemia: Report of a WHO/IDF Consultation (2006).
    • 20 Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of diet in renal disease study group. Ann. Intern. Med. 130(6), 461–470 (1999).
    • 21 Levey AS, Eckardt KU, Tsukamoto Y et al. Definition and classification of chronic kidney disease: a position statement from kidney disease: improving global outcomes. Kidney Int. 67(6), 2089–2100 (2005).
    • 22 Klen J, Goričar K, Janež A, Dolžan V. The role of genetic factors and kidney and liver function in glycemic control in Type 2 diabetes patients on long-term metformin and sulphonylurea cotreatment. BioMed Res. Int. 2014, 934729 (2014).
    • 23 Bohanec Grabar P, Logar D, Tomsic M, Rozman B, Dolzan V. Genetic polymorphisms of glutathione-S-transferases and disease activity of rheumatoid arthritis. Clin. Exp. Rheumatol. 27(2), 229–236 (2009).
    • 24 Chen CL, Liu Q, Relling MV. Simultaneous characterization of glutathione-S-transferase M1 and T1 polymorphisms by polymerase chain reaction in American whites and blacks. Pharmacogenetics 6(2), 187–191 (1996).
    • 25 Hodgkinson AD, Bartlett T, Oates PJ, Millward BA, Demaine AG. The response of antioxidant genes to hyperglycemia is abnormal in patients with Type 1 diabetes and diabetic nephropathy. Diabetes 52(3), 846–851 (2003).
    • 26 Flekac M, Skrha J, Hilgertova J, Lacinova Z, Jarolimkova M. Gene polymorphisms of superoxide dismutases and catalase in diabetes mellitus. BMC Med. Genet. 9, 30 (2008). • The study compared superoxide dismutase (SOD) and catalase genotype distribution in three relative big groups of T1D and T2D patients and controls.
    • 27 Panduru NM, Mota E, Mota M, Cimponeriu D, Serafinceanu C, Cheta DM. Polymorphism of catalase gene promoter in Romanian patients with diabetic kidney disease and Type 1 diabetes. Rom. J. Intern. Med. 48(1), 81–88 (2010).
    • 28 Neves AL, Mohammedi K, Emery N et al. Allelic variations in superoxide dismutase-1 (SOD1) gene and renal and cardiovascular morbidity and mortality in Type 2 diabetic subjects. Mol. Genet. Metab. 106(3), 359–365 (2012). •• Analysis of 7 single nucleotide polymorphisms (SNPs) in SOD1 region in 3744 T2D patients from the DIABHYCAR and DIABHYCAR_GENE cohorts.
    • 29 Gysin R, Kraftsik R, Boulat O et al. Genetic dysregulation of glutathione synthesis predicts alteration of plasma thiol redox status in schizophrenia. Antioxid. Redox. Signal. 15(7), 2003–2010 (2011).
    • 30 Willis AS, Freeman ML, Summar SR et al. Ethnic diversity in a critical gene responsible for glutathione synthesis. Free Radic. Biol. Med. 34(1), 72–76 (2003).
    • 31 Koide S, Kugiyama K, Sugiyama S et al. Association of polymorphism in glutamate-cysteine ligase catalytic subunit gene with coronary vasomotor dysfunction and myocardial infarction. J. Am. Coll. Cardiol. 41(4), 539–545 (2003).
    • 32 Nakamura S, Kugiyama K, Sugiyama S et al. Polymorphism in the 5'-flanking region of human glutamate-cysteine ligase modifier subunit gene is associated with myocardial infarction. Circulation 105(25), 2968–2973 (2002).
    • 33 Katakami N, Kaneto H, Matsuoka TA et al. Accumulation of gene polymorphisms related to oxidative stress is associated with myocardial infarction in Japanese Type 2 diabetic patients. Atherosclerosis 212(2), 534–538 (2010).
    • 34 Ramprasath T, Murugan PS, Kalaiarasan E, Gomathi P, Rathinavel A, Selvam GS. Genetic association of Glutathione peroxidase-1 (GPx-1) and NAD(P)H:Quinone Oxidoreductase 1 (NQO1) variants and their association of CAD in patients with Type 2 diabetes. Mol. Cell Biochem. 361(1–2), 143–150 (2012). • The study confirmed the association of GPx-1 and NQO1 variants with coronary artery disease (CAD) in patients with T2D.
    • 35 Amer MA, Ghattas MH, Abo-Elmatty DM, Abou-El-Ela SH. Evaluation of glutathione S-transferase P1 genetic variants affecting Type 2 diabetes susceptibility and glycemic control. Arch. Med. Sci. 8(4), 631–636 (2012).
    • 36 Moasser E, Kazemi-Nezhad SR, Saadat M, Azarpira N. Study of the association between glutathione S-transferase (GSTM1, GSTT1, GSTP1) polymorphisms with Type 2 diabetes mellitus in southern of Iran. Mol. Biol. Rep. 39(12), 10187–10192 (2012).
    • 37 Datta SK, Kumar V, Pathak R et al. Association of glutathione-S-transferase M1 and T1 gene polymorphism with oxidative stress in diabetic and nondiabetic chronic kidney disease. Ren. Fail. 32(10), 1189–1195 (2010). • The study reports association of GSTM1 and GSTT1 deletions with lower glutathione S-transferase (GST) levels and higher oxidative stress in both diabetic and nondiabetic patients with chronic kidney disease.
    • 38 Pinheiro DS, Rocha Filho CR, Mundim CA et al. Evaluation of glutathione-S-transferase GSTM1 and GSTT1 deletion polymorphisms on Type 2 diabetes mellitus risk. PLoS ONE 8(10), e76262 (2013).
    • 39 Cilensek I, Mankoc S, Petrovic MG, Petrovic D. GSTT1 null genotype is a risk factor for diabetic retinopathy in Caucasians with Type 2 diabetes, whereas GSTM1 null genotype might confer protection against retinopathy. Dis. Markers 32(2), 93–99 (2012).
    • 40 Kariz S, Nikolajevic Starcevic J, Petrovic D. Association of manganese superoxide dismutase and glutathione-S-transferases genotypes with myocardial infarction in patients with Type 2 diabetes mellitus. Diab. Res. Clin. Pract. 98(1), 144–150 (2012).
    • 41 Santl Letonja M, Letonja M, Ikolajevic-Starcevic JN, Petrovic D. Association of manganese superoxide dismutase and glutathione-S-transferases genotypes with carotid atherosclerosis in patients with diabetes mellitus Type 2. Int. Angiol. 31(1), 33–41 (2012).
    • 42 Vidan-Jeras B, Jurca B, Dolan V, Jeras M, Breskvar K, Bohinjec M. Slovenian Caucasian normal. In: HLA 1998. Terasaki PI, Gjertson DW (Eds). American Society for Histocompatibility and Immunogenetics, Kansas, USA (1998).
    • 43 Campos C. Chronic hyperglycemia and glucose toxicity: pathology and clinical sequelae. Postgrad. Med. 124(6), 90–97 (2012).
    • 44 Giugliano D, Ceriello A, Paolisso G. Oxidative stress and diabetic vascular complications. Diabetes Care 19(3), 257–267 (1996).
    • 45 Lyons TJ, Basu A. Biomarkers in diabetes: hemoglobin A1c, vascular and tissue markers. Transl. Res. 159(4), 303–312 (2012).
    • 46 Gnudi L. Cellular and molecular mechanisms of diabetic glomerulopathy. Nephrol. Dial. Transplant. 27(7), 2642–2649 (2012).
    • 47 Battisti WP, Palmisano J, Keane WE. Dyslipidemia in patients with Type 2 diabetes. relationships between lipids, kidney disease and cardiovascular disease. Clin. Chem. Lab. Med. 41(9), 1174–1181 (2003).
    • 48 Parati G, Bilo G, Ochoa JE. Benefits of tight blood pressure control in diabetic patients with hypertension: importance of early and sustained implementation of effective treatment strategies. Diabetes Care 34(Suppl. 2), S297–S303 (2011).
    • 49 Scarpioni R, Ricardi M, Albertazzi V, Melfa L. Treatment of dyslipidemia in chronic kidney disease: effectiveness and safety of statins. World. J. Nephrol. 1(6), 184–194 (2012).
    • 50 Jardine MJ, Hata J, Woodward M et al. Prediction of kidney-related outcomes in patients with Type 2 diabetes. Am. J. Kidney Dis. 60(5), 770–778 (2012).
    • 51 Jun M, Venkataraman V, Razavian M et al. Antioxidants for chronic kidney disease. Cochrane Database Syst. Rev. 10, CD008176 (2012).