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Diabetic nephropathy is the most common complication in patients with diabetes mellitus (DM) and is the major cause of end-stage renal disease. Oxidative stress contributes to the development of diabetic nephropathy. Superoxide dismutase 3 (SOD3), an extracellular antioxidant enzyme, catalyzes the dismutation of superoxide radicals into hydrogen peroxide and oxygen. Two SOD3 gene polymorphisms have been investigated in diverse ethnic population. The SOD3 rs2536512, a G to A single nucleotide polymorphism (SNP) results in the change of amino acid at position 58 (Ala to Thr) and has been associated with DM and hypertension. Both DM and hypertension are the major contributors for pathogenesis of diabetic nephropathy. The other SOD3 gene variant, rs2855262, (T>C SNP) is located on 3’untranslated region of the gene and has been studied in SOD3 haplotype analysis which suggested linkage disequilibrium (LD) with the upstream SNP, rs2536512. Down-regulation of renal SOD3 has been implicated in the pathogenesis of diabetic nephropathy in mouse model. The aim of this study was therefore to investigate the association of SOD3 gene polymorphisms, rs2536512 and rs2855262, with the risk of diabetic nephropathy in Thai DM patients. A total of 371 Thai DM patients (mean age 65.3±9.9 years; 181 DM patients with nephropathy and 190 DM patients without complication; matched for age and gender) were recruited. SOD3 gene polymorphisms (rs2536512 and rs2855262) were determined in genomic DNA using allele specific polymerase chain reaction (AS-PCR) technique. For rs2536512, the respective frequencies of G and A alleles in the study population were 61.5% and 38.5%. The frequencies of T and C alleles for rs2855262 were 57.4% and 42.6%. There were no significant differences of lipid parameters, fasting blood sugar (FBS), systolic blood pressure (SBP) and diastolic blood pressure (DBP) among genotype groups of each SOD3 SNP. For rs2536512, subjects with AA were associated with the increased risk of diabetic nephropathy (adjusted OR = 2.12; 95%CI 1.04-4.33) as compared with GG subjects. Although strong (D’=0.89) linkage disequilibrium (LD) was observed between these two studied SNPs, only marginal association with diabetic nephropathy were revealed for rs2855262 alone, combined two SNPs, and SOD3 haplotype [adjusted OR=1.84 (95%CI: 0.96-3.54), 2.03 (95%CI: 0.95-4.33), and 1.39 (95%CI: 0.99-1.95), respectively]. The present study demonstrated the association of SOD3 genetic variant, rs2536512, with the risk of diabetic nephropathy in Thai DM patients. |
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