title: Allelic variations in superoxide dismutase-1 (SOD1) gene are associated with increased risk of diabetic nephropathy in type 1 diabetic subjects.
abstract: 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.
authors.affiliation: INSERM, Research Unit 695, Paris, France.
authors.forename: Kamel
authors.initials: K
authors.lastname: Mohammedi
authors.forename: Suliya
authors.initials: S
authors.lastname: Maimaitiming
authors.forename: Nathalie
authors.initials: N
authors.lastname: Emery
authors.forename: Naima
authors.initials: N
authors.lastname: Bellili-Muñoz
authors.forename: Ronan
authors.initials: R
authors.lastname: Roussel
authors.forename: Frédéric
authors.initials: F
authors.lastname: Fumeron
authors.forename: Samy
authors.initials: S
authors.lastname: Hadjadj
authors.forename: Michel
authors.initials: M
authors.lastname: Marre
authors.forename: Gilberto
authors.initials: G
authors.lastname: Velho
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000201:enzymology* / Q000453:epidemiology; D003928:Diabetic Nephropathies / Q000201:enzymology* / Q000453:epidemiology / Q000209:etiology; D005260:Female; D056726:Genetic Association Studies; D014644:Genetic Variation; D005919:Glomerular Filtration Rate; D006239:Haplotypes; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D015995:Prevalence; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1; D055815:Young Adult
chemical_list: C000606290:SOD1 protein, human; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1