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 rs17880135 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.