Allelic variations in superoxide dismutase-1 (SOD1) gene and renal and cardiovascular morbidity and mortality in type 2 diabetic subjects

Oxidative stress is involved in the pathophysiology of renal and cardiovascular complications of diabetes. Superoxide dismutase (SOD) enzymes play a major role in detoxification of reactive oxygen species and protection against oxidative stress. Associations of SOD1 gene variants with diabetic nephropathy were reported in patients with type 1 diabetes. We investigated associations of allelic variations in SOD1 gene with nephropathy and cardiovascular complications in patients with type 2 diabetes. Seven SNPs in SOD1 region were analyzed in 3744 type 2 European Caucasian diabetic patients from the DIABHYCAR (a 6-year prospective study) and DIABHYCAR_GENE cohorts. Odds ratios or hazard ratios for prevalence and incidence of diabetic nephropathy and cardiovascular events were estimated. We observed an association of rs1041740 with the prevalence of microalbuminuria at baseline (OR 1.51, 95% CI 1.10–2.10, p=0.01). No association with the incidence of renal events (doubling of the serum creatinine levels or the requirement of hemodialysis or renal transplantation) or cardiovascular events (myocardial infarction or stroke) was observed during follow-up. However, three variants were associated with increased risk of death from cardiovascular causes (sudden death, fatal myocardial infarction or stroke) during the follow-up: rs9974610 (HR 0.64, 95% CI 0.46–0.88, p=0.005), rs10432782 (HR 1.71, 95% CI 1.16–2.48, p=0.007) and rs1041740 (HR 1.78, 95% CI 1.10–2.78, p=0.02). Our results are consistent with a major role for SOD1 in the mechanisms of cardiovascular protection against oxidative stress in type 2 diabetic subjects. ► Patients with type 2 diabetes followed prospectively for 6years. ► Impact of superoxide dismutase-1 (SOD1) gene variants on vascular complications. ► Allelic association with the prevalence of microalbuminuria at baseline. ► Allelic associations with increased risk of death from cardiovascular causes. ► Results consistent with SOD1 protection against oxidative stress.