title: The Impact of Superoxide Dismutase-1 Genetic Variation on Cardiovascular and All-Cause Mortality in a Prospective Cohort Study: The Yamagata (Takahata) Study.
abstract: BACKGROUND
  Oxidative stress is a major cause of cardiovascular disease. Superoxide dismutase-1 (SOD1) is an antioxidant that protects against oxidative stress. Deoxyribonucleic acid (DNA) variations such as single nucleotide polymorphism (SNP) or haplotypes within the SOD gene are reportedly associated with the development of cardiovascular disease. However, it remains to be determined whether SOD1 variability is associated with cardiovascular or all-cause mortality in the general population.
  
  
  RESULTS
  This prospective cohort study included 2799 subjects who participated in a community-based health study with a 10-year follow-up. We genotyped 639 SNPs and found the association of SNP rs1041740 and rs17880487 within a SOD1 gene with cardiovascular mortality. There were 193 deaths during the follow-up period including 57 cardiovascular deaths. Multivariate Cox proportional hazard regression analysis revealed that the homozygous T-allele of rs1041740 was associated with all-cause and cardiovascular deaths after adjusting for confounding factors. The net reclassification index was significantly improved by adding rs1041740 as a cardiovascular risk factor. On the other hand, cardiovascular death was not observed in homozygous T-allele carriers of rs17880487. Haplotype analysis identified the haplotype with T-allele of rs1041740 and that with T-allele of rs17880487 as increasing and decreasing susceptibility for cardiovascular mortality, and it had complementary SNP sequences.
  
  
  CONCLUSIONS
  Variation in the SOD1 gene was associated with cardiovascular deaths in the general population.
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Otaki
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Tetsu
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nishiyama
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Arimoto
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Shishido
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Miyamoto
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Konta
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Shibata
authors.affiliation: Genome Informatics Unit, Institute for Promotion of Medical Science Research, Faculty of Medicine, Yamagata University, Yamagata, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Sato
authors.affiliation: Department of Public Health, Graduate School of Medical Science, Yamagata University, Yamagata, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Kawasaki
authors.affiliation: Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, Aomori, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Daimon
authors.affiliation: Global Center of Excellence Program Study Group, Yamagata University School of Medicine; Yamagata, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Ueno
authors.affiliation: Global Center of Excellence Program Study Group, Yamagata University School of Medicine; Yamagata, Japan.
authors.forename: Takeo
authors.initials: T
authors.lastname: Kato
authors.affiliation: Global Center of Excellence Program Study Group, Yamagata University School of Medicine; Yamagata, Japan.
authors.forename: Takamasa
authors.initials: T
authors.lastname: Kayama
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Kubota
mesh_terms: D000368:Aged; D000483:Alleles; D002318:Cardiovascular Diseases / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D002423:Cause of Death; D015331:Cohort Studies; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D000072105:Superoxide Dismutase-1 / Q000235:genetics*
chemical_list: D000072105:Superoxide Dismutase-1