title: Genetically Low Antioxidant Protection and Risk of Cardiovascular Disease and Heart Failure in Diabetic Subjects.
abstract: BACKGROUND
  Hyperglycemia-induced oxidative stress is one mechanism believed to underlie diabetic vascular disease. We tested the hypothesis that diabetic subjects heterozygous for extracellular superoxide dismutase (SOD3) R213G, which entails lower antioxidant capacity in tissues, have increased risk of cardiovascular disease and heart failure.
  
  
  METHODS
  We used the prospective Copenhagen General Population Study and Copenhagen City Heart Study and genotyped 95,871 individuals for the rs1799895 R213G variation in the SOD3 gene, of which 4498 had diabetes. We used national hospitalization and death registers to assess cardiovascular disease and heart failure.
  
  
  RESULTS
  Out of 95,871 individuals, we identified 93,521 R213G non-carriers (213RR, 97.5%), 2336 heterozygotes (213RG, 2.4%) and 14 homozygotes (213GG, 0.01%). In diabetic subjects, the hazard ratio for cardiovascular disease in R213G heterozygotes compared to non-carriers was 2.32 (95% CI 1·44-3.75), with a corresponding hazard ratio in non-diabetic subjects of 0.97 (0·80-1.19) (p for interaction 0.002). For heart failure, the hazard ratios in R213G heterozygotes compared to non-carriers were 2.19 (1.28-3.76) in diabetic and 0.68 (0.49-0.92) in non-diabetic subjects (p for interaction < 0.001).
  
  
  CONCLUSIONS
  Risk of cardiovascular disease and heart failure was higher in R213G heterozygotes versus non-carriers in diabetic subjects, but not in non-diabetic subjects.
authors: Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev Ringvej 75, DK-2730 Herlev, Denmark.
authors: Camilla J
authors: CJ
authors: Kobylecki
authors: Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, 2100 Copenhagen, Denmark.
authors: Shoaib
authors: S
authors: Afzal
authors: Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev Ringvej 75, DK-2730 Herlev, Denmark.
authors: Børge G
authors: BG
authors: Nordestgaard
mesh_terms: D000368:Aged; D000975:Antioxidants / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000209:etiology*; D003718:Denmark / Q000453:epidemiology; D048909:Diabetes Complications / Q000453:epidemiology*; D003920:Diabetes Mellitus / Q000453:epidemiology*; D005260:Female; D020022:Genetic Predisposition to Disease; D006333:Heart Failure / Q000453:epidemiology* / Q000209:etiology*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012306:Risk; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism
chemical_list: D000975:Antioxidants; D013482:Superoxide Dismutase
keywords: Cardiovascular disease; Diabetes; Oxidative stress; Superoxide dismutase 3