Journal Article

The Impact of Superoxide Dismutase-1 Genetic Variation on Cardiovascular and All-Cause Mortality in a Prospective Cohort Study: The Yamagata (Takahata) Study

Kawasaki, Ryo, Watanabe, Tetsu, Shishido, Tetsuro, Miyamoto, Takuya, Shibata, Yoko, Kubota, Isao, Takahashi, Hiroki, Konta, Tsuneo, Arimoto, Takanori, Ueno, Yoshiyuki, Kato, Takeo, Daimon, Makoto, Sato, Hidenori, Kayama, Takamasa, Otaki, Yoichiro, Nishiyama, Satoshi

2016

Overview

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. 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. Variation in the SOD1 gene was associated with cardiovascular deaths in the general population.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Aged / Alleles / Analysis / Antioxidants / Antioxidants (Nutrients) / Biology and Life Sciences / Cardiology / Cardiovascular disease / Cardiovascular diseases / Cardiovascular Diseases - genetics / Cardiovascular Diseases - mortality / Cardiovascular Diseases - pathology / Cause of Death / Cholesterol / Cohort analysis / Cohort Studies / Community involvement / Community participation / Deoxyribonucleic acid / Diabetes / DNA / Fatalities / Female / Gene polymorphism / Gene sequencing / Genetic aspects / Genetic diversity / Genetic Variation / Genotype / Haplotypes / Health aspects / Health risk assessment / Health risks / Heart failure / Humans / Kaplan-Meier Estimate / Male / Medicine / Medicine and Health Sciences / Middle Aged / Mortality / Nephrology / Nucleic acids / Oxidative stress / Peptides / Physical Sciences / Polymorphism / Polymorphism, Single Nucleotide / Population / Proportional Hazards Models / Prospective Studies / Public health / Reclassification / Regression analysis / Research and Analysis Methods / Risk Factors / Rodents / Single nucleotide polymorphisms / Single-nucleotide polymorphism / Sod gene / Superoxide dismutase / Superoxide Dismutase-1 - genetics / Superoxides / Variation