Allelic variations in superoxide dismutase-1 (SOD1) gene are associated with increased risk of diabetic nephropathy in type 1 diabetic subjects

Background: Oxidative stress is involved in the pathophysiology of diabetic nephropathy. The superoxide dismutase (SOD) enzymes play a major role in detoxification of reactive oxygen species and have a protective effect against diabetic nephropathy. We investigated associations of allelic variations in SOD1 gene with nephropathy in patients with type 1 diabetes. Methods: Seven SNPs in SOD1 region were analyzed in 1285 type 1 European Caucasian diabetic patients from the SURGENE prospective study (n =340; ten year follow-up), and the Genesis France-Belgium (n = 501) and GENEDIAB (n=444) cross-sectional studies. Cox proportional hazards and logistic regression analyses were used to estimate hazard ratios or odds ratios for incidence and prevalence of diabetic nephropathy. Results: In the SURGENE study, the T-allele of rs1041740 was associated with the prevalence of incipient (OR 5.75, 95% CI 1.78-19.39, p= 0.004) and established/advanced nephropathy at baseline (OR 8.95, 95% CI 1.51-58.42, p = 0.02), and with the incidence of incipient nephropathy during follow-up (HR 1.46, 95% C.I. 1.13-1.90, p =0.004). The variant was also associated with decreased estimated glomerular filtration rate (eGFR) throughout the study. In cross-sectional study of Genesis/GENEDIAB cohorts, the G-allele of rs1 7880135 was associated with incipient (OR 7.53,95% CI 2.30-25.45, p = 0.001), established (OR 6.04,95% CI 1.52-23.91, p = 0.01) and advanced nephropathy (OR 10.03, 95% CI 2.95-35.44, p= 0.0003). Conclusions: SOD1 allelic variations were associated with the prevalence of diabetic nephropathy, with the incidence of microalbuminuria and with decreased eGFR in type 1 diabetic subjects. These results are consistent with an implication of oxidative stress in the pathophysiology of diabetic nephropathy and with the major role for antioxidant enzymes as a mechanism of renal protection. (C) 2011 Elsevier Inc. All rights reserved.