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From SNPedia

Geno Mag Summary
(C;C) 1.1 complex! see rs4880
(C;T) 1.1 complex! see rs4880
(T;T) 1.1 complex! see rs4880
ReferenceGRCh38 38.1/141
is asnp
is mentioned by
dbSNP (classic)rs4880
1000 genomesrs4880
GWAS Ctlgrs4880
Merged fromRs1799725
Max Magnitude1.1
? (C;C) (C;T) (T;T) 28

The rs4880(T) allele, part of the codon for amino acid valine at codon 16 of the antioxidant protein from the mitochrondrial superoxide dismutase 2 SOD2 gene, is the most common in most populations studied. The rs4880(C) allele gives rise to an alanine at this position is it also known as Val16Ala manganese superoxide dismutase, or A16V.

There appears to be some conflict in the literature over the effect of this SNP. Having a valine at codon 16 is said to reduce enzyme activity [PMID 15864132], and thus lead to increased oxidative stress, yet in at least one study of the actual enzyme levels measured in people, SOD2 activity was 33% higher in (C;T) or (T;T) individuals compared to (C;C) individuals [PMID 16538174]. Regardless of how this resolves, several phenotypic associations have been reported for this SNP, including:

  • An increased risk of malignant pleural mesothelioma (MPM) was found in individuals with rs4880(C;C) (OR = 3.07, CI: 1.55-6.05) genotypes. Odds ratios for developing mesothelioma were even higher for patients lacking obvious exposure to asbestos fibers. [PMID 17290392]
  • Among prostate cancer patients with a rs4880(T;T) genotype, but not the (C;C) genotype, higher iron intake level was associated with a 2.3-fold increase in risk for aggressive forms of the cancer (OR=2.3, CI: 1.0-4.9).[PMID 18296681OA-icon.png]
  • rs4880(C;T) prostate cancer patients being treated by radiation therapy are more likely (8% compared to 0%, p=0.02) to exhibit a significant increase in grade 2 late rectal bleeding after irradiation than (C;C) or (T;T) patients, based on a study of 135 patients. The odds for this are worse if the patient also has the rs861539(C;T) genotype (14% vs 1%, p=0.002).[PMID 18582155]
  • A study of non-Hispanic Caucasians with various types of brain tumors concluded that there was an increased risk of acoustic neuroma (odds ratio 2.0, CI: 1.1-2.7) associated with the alanine-encoding rs4880(C) allele.[PMID 18682580OA-icon.png]
  • rs4880(C) carriers with breast cancer and being treated with cyclophosphamide had worse survival rates (i.e. didn't benefit as much), based on a 2009 study of 248 US and 340 Norwegian patients.[PMID 19509150OA-icon.png]
    • A 2010 US study of ~450 women receiving cyclophosphamide + adjuvant therapy concluded that rs4880(C) carriers suffered slightly less side effects (HR 0.5) but had slightly worse disease-free survival rates (DFS 1.6); no associations were observed among 874 women who were followed without adjuvant therapy {{PMID


    • A 2014 Danish meta-analysis plus study of ~300 patients receiving cyclophosphamide chemotherapy found no association with rs4880(C) genotype [PMID 24498107OA-icon.png]
    • A 2015 study with a relatively small number (~500) of Chinese gastric cancer patients found rs4880(C) carriers who received postoperative platinum and fluorouracil based chemotherapy were somewhat worse off than non-carriers [PMID 25901207OA-icon.png]

The C allele of rs4880 appears to be slightly associated with Alzheimer's disease. [PMID 17376152] rs2758346 rs4880 and rs2855116 association with Alzheimer's disease

[PMID 19493484] Association between SNPs in SOD2 and noise-induced hearing loss


[PMID 19706356] Functional polymorphism in manganese superoxide dismutase and antioxidant status: Their interactions on the risk of cervical intraepithelial neoplasia and cervical cancer

[PMID 19753309OA-icon.png] SOD2 gene polymorphisms in neovascular age-related macular degeneration and polypoidal choroidal vasculopathy

[PMID 19778569] Oxidative stress in tardive dyskinesia: Genetic association study and meta-analysis of NADPH quinine oxidoreductase 1 (NQO1) and Superoxide dismutase 2 (SOD2, MnSOD) genes

[PMID 19863340] Influence of the polymorphism in candidate genes on late cardiac damage in patients treated due to acute leukemia in childhood

[PMID 20043000OA-icon.png] Association of SOD2, a Mitochondrial Antioxidant Enzyme, with Gray Matter Volume Shrinkage in Alcoholics

[PMID 20082738] Inter-individual variation in DNA damage and base excision repair in young, healthy non-smokers: effects of dietary supplementation and genotype

[PMID 20534900OA-icon.png] SOD2 V16A SNP in the mitochondrial targeting sequence is associated with noise induced hearing loss in Chinese workers

[PMID 20378690] Genetic variants in selenoprotein genes increase risk of colorectal cancer

[PMID 21062213] Manganese superoxide dismutase dimorphism relationship with severity and prognosis in cardiogenic shock due to dilated cardiomyopathy


[PMID 21567099] Estrogen metabolism genotypes, use of long-term hormone replacement therapy and risk of postmenopausal breast cancer

[PMID 21795425OA-icon.png] Genetic Variation in Myeloperoxidase Modifies the Association of Serum {alpha}-Tocopherol with Aggressive Prostate Cancer among Current Smokers

[PMID 21915362OA-icon.png] Sequence variants in antioxidant defense and DNA repair genes, dietary antioxidants, and pancreatic cancer risk

[PMID 22144047OA-icon.png] A single-nucleotide polymorphism in the MTHFR (methylene tetrahydrofolate reductase) gene is associated with risk of radiation pneumonitis in lung cancer patients treated with thoracic radiation therapy

[PMID 22206979] Genetic variants in antioxidant genes are associated with sperm DNA damage and risk of male infertility in a Chinese population

[PMID 21338322] Parameters of oxidative stress, DNA damage and DNA repair in type 1 and type 2 diabetes mellitus

[PMID 21351093] Association of superoxide dismutases and NAD(P)H quinone oxidoreductases with prognosis of patients with breast carcinomas

Risk Rs4880(C;C)
Alt Rs4880(C;C)
Reference Rs4880(T;T)
Significance Other
Disease SUPEROXIDE DISMUTASE 2 POLYMORPHISM Microvascular complications of diabetes 6 cyclophosphamide response - Efficacy
Variation info
Gene SOD2
CLNDBN SUPEROXIDE DISMUTASE 2 POLYMORPHISM Microvascular complications of diabetes 6 cyclophosphamide response - Efficacy
Reversed 1
HGVS NC_000006.11:g.160113872A>G
CLNSRC OMIM Allelic Variant PharmGKB Clinical Annotation
CLNACC RCV000015872.2, RCV000015873.2, RCV000211191.1,

[PMID 16385446OA-icon.png] A testing framework for identifying susceptibility genes in the presence of epistasis.

[PMID 16543247] Polymorphisms in oxidative stress genes and risk for non-Hodgkin lymphoma.

[PMID 16945136OA-icon.png] Gene x Gene interaction between MnSOD and GPX-1 and breast cancer risk: a nested case-control study.

[PMID 17293864] A common coding variant in CASP8 is associated with breast cancer risk.

[PMID 17601350OA-icon.png] A genetic association analysis of cognitive ability and cognitive ageing using 325 markers for 109 genes associated with oxidative stress or cognition.

[PMID 17825092OA-icon.png] Genetic association of glutathione peroxidase-1 with coronary artery calcification in type 2 diabetes: a case control study with multi-slice computed tomography.

[PMID 18191955OA-icon.png] Correlating observed odds ratios from lung cancer case-control studies to SNP functional scores predicted by bioinformatic tools.

[PMID 18212354OA-icon.png] Genes in glucose metabolism and association with spina bifida.

[PMID 18340529OA-icon.png] A prospective study of genetic polymorphism in MPO, antioxidant status, and breast cancer risk.

[PMID 18423055OA-icon.png] Gene polymorphisms of superoxide dismutases and catalase in diabetes mellitus.

[PMID 18676870OA-icon.png] Variants in inflammation genes and the risk of biliary tract cancers and stones: a population-based study in China.

[PMID 18698231OA-icon.png] Polymorphisms affecting gene transcription and mRNA processing in pharmacogenetic candidate genes: detection through allelic expression imbalance in human target tissues.

[PMID 18704161OA-icon.png] Genetic variation in an individual human exome.

[PMID 18781856] Genetic underpinnings of tardive dyskinesia: passing the baton to pharmacogenetics.

[PMID 19074884OA-icon.png] Interaction between single nucleotide polymorphisms in selenoprotein P and mitochondrial superoxide dismutase determines prostate cancer risk.

[PMID 19428448OA-icon.png] The Mn-superoxide dismutase single nucleotide polymorphism rs4880 and the glutathione peroxidase 1 single nucleotide polymorphism rs1050450 are associated with aging and longevity in the oldest old.

[PMID 19505917OA-icon.png] Lead exposure, polymorphisms in genes related to oxidative stress, and risk of adult brain tumors.

[PMID 19754948OA-icon.png] Evaluation of nine candidate genes in patients with normal tension glaucoma: a case control study.

[PMID 19946932] Lack of association of GPX1 and MnSOD genes with symptom severity and response to clozapine treatment in schizophrenia subjects.

[PMID 20444272OA-icon.png] Gene polymorphisms against DNA damage induced by hydrogen peroxide in leukocytes of healthy humans through comet assay: a quasi-experimental study.

[PMID 20445800OA-icon.png] Genetic Polymorphisms in Genes Related to Oxidative Stress (GSTP1, GSTM1, GSTT1, CAT, MnSOD, MPO, eNOS) and Survival of Rectal Cancer Patients after Radiotherapy.

[PMID 20477822OA-icon.png] Single-nucleotide polymorphisms within the antioxidant defence system and associations with aggressive prostate cancer.

[PMID 20644561] A large-scale candidate gene approach identifies SNPs in SOD2 and IL13 as predictive markers of response to preoperative chemoradiation in rectal cancer.

[PMID 20728955] Association between the rs4880 superoxide dismutase 2 (C>T) gene variant and coronary heart disease in diabetes mellitus.

[PMID 20872977OA-icon.png] Mn-SOD and CuZn-SOD polymorphisms and interactions with risk factors in gastric cancer.

[PMID 20966810] Superoxide dismutase and nicotinamide adenine dinucleotide phosphate: quinone oxidoreductase polymorphisms and pancreatic cancer risk.

[PMID 21181397] Association of the C47T polymorphism in SOD2 with diabetes mellitus and diabetic microvascular complications: a meta-analysis.

[PMID 21240526] Evaluation of the association studies of single nucleotide polymorphisms and hepatocellular carcinoma: a systematic review.

[PMID 21595856] Genetic polymorphisms in antioxidative enzymes are associated to forced expiratory volume in 1 s (FEV1) in smokers independently of asthma.

[PMID 21741706] Correlation of CYP2B6, CYP2C19, ABCC4 and SOD2 genotype with outcomes in allogeneic blood and marrow transplant patients.

[PMID 21756849] The SOD2 C47T polymorphism influences NAFLD fibrosis severity: evidence from case-control and intra-familial allele association studies.

[PMID 22531667] PM10-induced hospital admissions for asthma and chronic obstructive pulmonary disease: the modifying effect of individual characteristics.

[PMID 22564066] Heterocyclic Aromatic Amine [HCA] Intake and Prostate Cancer Risk: Effect Modification by Genetic Variants.

[PMID 22574884] Genetic polymorphisms of antioxidant enzymes as risk factors for oxidative stress-associated complications in preterm infants.

[PMID 22661588OA-icon.png] Antioxidant enzyme polymorphisms and neuropsychological outcomes in medulloblastoma survivors: a report from the Childhood Cancer Survivor Study.

[PMID 22615781OA-icon.png] Candidate gene-based association study of antipsychotic-induced movement disorders in long-stay psychiatric patients: a prospective study

[PMID 23142385] Frequency of sepsis in patients with the 47C allele of SOD2 gene

[PMID 23500038] A Functional and Genetic Analysis of SOD2 Promoter Variants and their Contribution to Age-Related Hearing Loss

[PMID 23647424] Association of Mn-SOD Mutation (c.47T > C) with Various POAG Clinical Indices

[PMID 24070129] Association of SOD2 Mutation (c.47T\gtC) with Various Primary Angle Closure Glaucoma Clinical Indices

[PMID 24348785OA-icon.png] Correlation between superoxide dismutase 1 and 2 polymorphisms and susceptibility to oral squamous cell carcinoma

[PMID 24119114OA-icon.png] SOD2 gene Val16Ala polymorphism is associated with macroalbuminuria in Mexican type 2 diabetes patients: a comparative study and meta-analysis

[PMID 24499375] Association of Oxidative Stress Related Genes with Idiopathic Recurrent Miscarriage

[PMID 24552298OA-icon.png] Association Between Six Genetic Polymorphisms and Colorectal Cancer: A Meta-Analysis

[PMID 24586301OA-icon.png] No Association of Four Candidate Genetic Variants in MnSOD and SYNIII with Parkinson's Disease in Two Chinese Populations

[PMID 24610081] Associations Between SNPs Within Antioxidant Genes and the Risk of Prostate Cancer in the Siberian Region of Russia

[PMID 22517484] Clinical significance of SOD2 and GSTP1 gene polymorphisms in Chinese patients with gastric cancer.

[PMID 22610343OA-icon.png] Genetic variants in antioxidant genes are associated with diisocyanate-induced asthma.

[PMID 22877234OA-icon.png] Polymorphisms in genes involved in oxidative stress response in patients with sudden sensorineural hearing loss and Meniere's disease in a Japanese population.

[PMID 22958044] Genetic polymorphisms of antioxidant enzymes in preterm infants.

[PMID 22987024] Aromatic DNA adducts and number of lung cancer risk alleles in Map-Ta-Phut Industrial Estate workers and nearby residents.

[PMID 23175176OA-icon.png] Variation in PAH-related DNA adduct levels among non-smokers: the role of multiple genetic polymorphisms and nucleotide excision repair phenotype.

[PMID 23261794] Influence of genetic polymorphisms on the association between phthalate exposure and pulmonary function in the elderly.

[PMID 24865797] SOD2 gene polymorphism and muscle damage markers in elite athletes

[PMID 24919441OA-icon.png] Polymorphisms of NRF2 and NRF2 target genes in urinary bladder cancer patients

[PMID 24036105] Involvement of superoxide dismutase isoenzymes and their genetic variants in progression of and higher susceptibility to vitiligo

[PMID 25497738] Effect of 593C>T GPx1 SNP alone and in synergy with 47C>T SOD2 SNP on the outcome of critically ill patients

[PMID 25901207OA-icon.png] SOD2 rs4880 CT/CC genotype predicts poor survival for Chinese gastric cancer patients received platinum and fluorouracil based adjuvant chemotherapy

[PMID 25417767] Association of SOD2 polymorphisms with primary open angle glaucoma in a Chinese population

[PMID 25573779] Host genetic variations in glutathione-S-transferases, superoxide dismutases and catalase genes influence susceptibility to malaria infection in an Indian population

[PMID 26400460OA-icon.png] SOD2 genetic variant associated with treatment-related ototoxicity in cisplatin-treated pediatric medulloblastoma

[PMID 24517502] Gene variants encoding proteins involved in antioxidant defense system and the clinical expression of Wilson disease

[PMID 26446998OA-icon.png] Lipid peroxidation and glutathione peroxidase activity relationship in breast cancer depends on functional polymorphism of GPX1

[PMID 26505452] Polymorphic variations in manganese superoxide dismutase (MnSOD) and endothelial nitric oxide synthase (eNOS) genes contribute to the development of type 2 diabetes mellitus in the Chinese Han population

[PMID 26696693OA-icon.png] Association of the C47T Polymorphism in SOD2 with Amnestic Mild Cognitive Impairment and Alzheimer's Disease in Carriers of the APOEε4 Allele.

[PMID 27141263OA-icon.png] Role of Superoxide Dismutase 2 Gene Ala16Val Polymorphism and Total Antioxidant Capacity in Diabetes and its Complications.

[PMID 28711952] Polymorphic variants of antioxidative defense enzymes and their gene-gene epistatic interactions in systemic lupus erythematode patients.

[PMID 27019981OA-icon.png] Expression and polymorphism (rs4880) of mitochondrial superoxide dismutase (SOD2) and asparaginase induced hepatotoxicity in adult patients with acute lymphoblastic leukemia.

[PMID 29331597] Variation of genes involved in oxidative and nitrosative stresses in depression.

[PMID 29655960] Systemic redox biomarkers and their relationship to prognostic risk markers in autosomal dominant polycystic kidney disease and IgA nephropathy.

[PMID 29681991OA-icon.png] The relationship between MnSOD Val16Ala gene polymorphism and the level of serum total antioxidant capacity with the risk of chronic kidney disease in type 2 diabetic patients: a nested case-control study in the Tehran lipid glucose study.

[PMID 29745991] Association of pre-eclampsia with SOD2 Ala16Val polymorphism among mother-father-infant triads.

[PMID 30191955] Association of polymorphisms in genes coding for antioxidant enzymes and human male infertility.

[PMID 31647334] Impact of oxidative stress SNPs and dietary antioxidant quality score on prostate cancer.

[PMID 31905014] Investigation of Oxidative Stress-Related Candidate Genes as Risk Factors for Drug-Induced Liver Injury due to Co-Amoxiclav.

[PMID 32295184OA-icon.png] MTHFR and VDR Polymorphisms Improve the Prognostic Value of MYCN Status on Overall Survival in Neuroblastoma Patients.

[PMID 32885455OA-icon.png] The Impact of MnSOD and GPx1 Genotype at Different Levels of Enteral Nutrition Exposure on Oxidative Stress and Mortality: A Post-hoc Analysis from the FeDOx Trial.