Association among extracellular superoxide dismutase genotype, plasma concentration, and comorbidity in the very old and centenarians

• Published in: Scientific reports Vol. 11; no. 1; p. 8539
• Main Authors: Sasaki, Takashi, Abe, Yukiko, Takayama, Michiyo, Adachi, Tetsuo, Okano, Hideyuki, Hirose, Nobuyoshi, Arai, Yasumichi
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 20.04.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/208/2489; 631/208/727; 692/308/53; Adiponectin; Age; Aging; Antioxidants; Comorbidity; Creatinine; Diabetes mellitus; Genomes; Genotype & phenotype; Genotypes; Geriatrics; Glomerular filtration rate; Humanities and Social Sciences; Kidney diseases; multidisciplinary; Oldest old people; Plasma; Science; Science (multidisciplinary); Superoxide dismutase
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-87982-6

Superoxide dismutase 3 ( SOD3 ), an antioxidant enzyme, is known as extracellular SOD (EC-SOD) because it is the predominant form in extracellular fluids. The diversity of plasma EC-SOD concentration is associated with the SOD3 p.R231G missense variant genotype. To clarify the association among SOD3 genotype, plasma EC-SOD concentration, and comorbidity in Oldest Old, we analyzed genome-wide associations with plasma EC-SOD concentration and associations between EC-SOD concentration and medical history classified by the SOD3 genotype in the Very Old (85–99 years old, n = 505) and Centenarians (over 100 years old, n = 595). The results revealed that SOD3 p.R231G was the most significant variant associated with plasma EC-SOD concentration. Although no significant difference was observed in medical histories between the SOD3 p.R231G variant non-carriers and carriers, higher EC-SOD concentration in plasma of SOD3 p.R231G variant non-carriers was associated with a high odds ratio for chronic kidney disease (OR = 2.70, 95% CI = 1.98–3.72) and low odds ratio for diabetes mellitus (DM) (OR = 0.61, 95% CI = 0.39–0.95). Comparison with 11 plasma biomarkers for age-related disease showed that plasma EC-SOD concentration correlated with adiponectin and estimated glomerular filtration rate with creatinine correction; therefore, we deduced that EC-SOD co-operates with adiponectin and possesses beneficial functions for DM in the Oldest Old.