LongevityMap Gene

Gene details

HGNC symbol: SOD2
Aliases: IPOB; IPO-B; MNSOD; MVCD6; Mn-SOD
Common name: superoxide dismutase 2
Description: This gene is a member of the iron/manganese superoxide dismutase family. It encodes a mitochondrial protein that forms a homotetramer and binds one manganese ion per subunit. This protein binds to the superoxide byproducts of oxidative phosphorylation and converts them to hydrogen peroxide and diatomic oxygen. Mutations in this gene have been associated with idiopathic cardiomyopathy (IDC), premature aging, sporadic motor neuron disease, and cancer. Alternative splicing of this gene results in multiple transcript variants. A related pseudogene has been identified on chromosome 1. [provided by RefSeq, Apr 2016]
Cytogenetic Location: 6q25.3
UCSC Genome Browser: View 6q25.3 on the UCSC genome browser
OMIM: 147460
Ensembl: ENSG00000112096
UniProt/Swiss-Prot: A0A0C4DFU1_HUMAN
Entrez Gene: 6648
UniGene: 487046
1000 Genomes: 1000 Genomes

Homologs in model organisms

Caenorhabditis elegans: sod-2
Caenorhabditis elegans: sod-3
Danio rerio: sod2
Drosophila melanogaster: Sod2
Mus musculus: Sod2
Rattus norvegicus: Sod2
Saccharomyces cerevisiae: SOD2
Schizosaccharomyces pombe: SPBC16A3.14

In other databases

GenAge model organism genes

A homolog of this gene for Saccharomyces cerevisiae is present as SOD2
A homolog of this gene for Drosophila melanogaster is present as Sod2
A homolog of this gene for Mus musculus is present as Sod2
A homolog of this gene for Caenorhabditis elegans is present as sod-2

GenAge human genes

This gene is present as SOD2

GenDR gene manipulations

A homolog of this gene for Saccharomyces cerevisiae is present as SOD2

CellAge

This gene is present as SOD2

Studies (9)

Significant/Non-significant: 3/6

Study 1

Longevity Association

Non-significant

Population

Study Design

401C/T SNP was examined in 196 centenarians (143 females and 53 males) and 358 controls (196 females and 162 male; 10-85 years old)

Conclusions

No significant difference in genotypic frequencies was found between centenarians and controls

Indentifier

Reference

Study 2

Longevity Association

Non-significant

Population

Ashkenazi Jewish (Jerusalem)

Study Design

C9T, Ala (GCT) to Val (GTT), SNP was examined in 224 older (75 years) Jewish Jerusalem residents of Ashkenazi ethnicity (150 males and 74 females) and a group of 441 younger subjects (22 years)

Conclusions

There was an increase in the percentage of T allele (51% versus 33.3%) in older Ashkenazi male subjects and a corresponding increase in the percentage (45.5% versus 25%) of TT homozygotes, though this was not significant after correcting for multiple testing

Indentifier

Reference

Study 3

Longevity Association

Non-significant

Population

Study Design

Exon 16 C/T SNP was examined in 1576 individuals aged >85

Conclusions

No association with reduced mortality risk was found

Indentifier

Reference

Study 4

Longevity Association

Non-significant

Population

Study Design

Polymorphisms were genotyped in 130 elderly subjects (57 females, mean age: 90.01 years) and 135 young control subjects (67 females, mean age: 33.43 years) for longevity association

Conclusions

No significant differences were found in the genotype and allele frequencies of examined SOD2 and MTHFR gene variants between the elderly group and young controls (P > 0.05), nor when each gender was considered separately (P > 0.05). SOD2 -9T/C and MTHFR 677C/T were not associated with longevity in the Jordanian population.

Indentifier

Reference

Study 5

Longevity Association: Significant
Population: Danish
Study Design: SNPs rs4880 in MnSOD and rs1050450 in GPX1 were genotyped in 1650 individuals from the Danish 1905 cohort (follow-up time: 1998–2008, age at intake: 92–93 years, number of deaths: 1589 (96.3%)) and investigated for the association with aging and longevity
Conclusions: Decreased mortality of individuals holding either the MnSOD rs4880 C or the GPX1 rs1050450 T alleles (HR (MnSOD(CC/CT)) = 0.91, p = 0.002), HR (GPX1(TT/TC)) = 0.93, p = 0.008)) was observed, as well as a synergetic effect (HR = 0.76, p = 0.001). Genetic variation in MnSOD and GPX1 may be associated with aging and longevity.
Indentifier

Study 6

Longevity Association: Significant
Population: American (Caucasian)
Study Design: Genome-wide association study in 801 centenarians and 914 healthy controls
Conclusions: 281 SNPs were found to discriminate between cases and controls
Indentifier

Study 7

Longevity Association: Significant
Population: Danish
Study Design: 38 genes (311 SNPs) belonging to pro-antioxidant pathways were investigated for the association with physical and cognitive performances in a Cohort of 1089 Danish nonagenarians. For each gene analyzed in the pro-antioxidant pathway, the influence on longitudinal survival was tested.
Conclusions: NDUFS1, TXNRD1, SOD2 and UCP3 were found significantly associated with lifespan in the female cohort. This result is consistent with their associations with physical functioning and suggests that the variability of genes in the pro-antioxidant pathway can influence survival through an effect on physical performances, at least in the analyzed cohort.
Indentifier

Study 8

Longevity Association: Non-significant
Population: German
Study Design: 19 SNPs were examined in 1612 long-lived individuals (centenarians and nonagenarians) and 1104 younger controls as well as a subgroup of 748 centenarians from 1612 LLIs and 1104 younger controls.
Conclusions: No association was detected between the tested SNPs and the longevity phenotype, in the entire long-lived sample set nor in the centenarian subgroup analysis. There was no considerable influence of sequence variation in the SOD genes on human longevity in Germans.
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Study 9

Longevity Association: Non-significant
Population: Italian (Southern)
Study Design: A two-stage case-control study was performed to identify the association between longevity and variation of in homeostasis regulation pathway genes. 317 SNPs in 104 genes were analyzed in 78 cases (≥90 years, median age 98 years, 42 females) and 71 controls (<90 years, median age 67 years, 32 females) in stage 1. Then, 31 candidate SNPs identified in stage 1 (π markers = 0.1) were analyzed in an independent sample composed by 288 cases (≥90 years, median age 92 years, 163 females) and 554 controls (<90 years, median age 67 years, 277 females).
Conclusions: After adjustment for multiple testing, no significant association was identified between various SNPs and longevity.
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