{{Rsnum
|rsid=4880
|Gene=SOD2
|Chromosome=6
|position=159692840
|Orientation=minus
|ReferenceAllele=T
|MissenseAllele=C
|GMAF=0.3705
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|geno1=(C;C)
|geno2=(C;T)
|geno3=(T;T)
|Gene_s=SOD2
}}{{ population diversity
| geno1=(C;C)
| geno2=(C;T)
| geno3=(T;T)
| CEU | 22.1 | 45.1 | 32.7
| HCB | 1.5 | 22.8 | 75.7
| JPT | 1.8 | 15.9 | 82.3
| YRI | 14.3 | 47.6 | 38.1
| ASW | 10.7 | 50.0 | 39.3
| CHB | 1.5 | 22.8 | 75.7
| CHD | 2.8 | 21.1 | 76.1
| GIH | 22.8 | 50.5 | 26.7
| LWK | 20.4 | 47.2 | 32.4
| MEX | 38.6 | 50.9 | 10.5
| MKK | 14.1 | 58.3 | 27.6
| TSI | 22.5 | 48.0 | 29.4
| HapMapRevision=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:

* A 10 fold higher risk for [[heart disease]] in hereditary [[hemochromatosis]] patients with [[rs4880]](T;T) genotypes compared to similar patients with [[rs4880]](C;T) or [[rs4880]](C;C) genotypes. {{PMID|15591282|OA=1
}}

* 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|18296681|OA=1
}}

* [[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|18682580|OA=1
}}

* [[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 study of 248 US and 340 Norwegian patients.{{PMID|19509150|OA=1
}} 

* See also [http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147460&a=147460_AllelicVariant0001 OMIM 147460.0001]

* Note: [[rs1799725]] was combined into [[rs4880]] by [[dbSNP]]

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

{{ neighbor
| rsid = 1799725
| distance = 1
}}

{{PMID Auto
|PMID=19493484
|Title=Association between SNPs in SOD2 and noise-induced hearing loss
}}

{{omim
|id=612634
|desc=MICROVASCULAR COMPLICATIONS OF DIABETES, SUSCEPTIBILITY TO, 6; MVCD6
|rsnum=4880
}}
{{PMID Auto
|PMID=19706356
|Title=Functional polymorphism in manganese superoxide dismutase and antioxidant status: Their interactions on the risk of cervical intraepithelial neoplasia and cervical cancer
}}
{{PMID Auto
|PMID=19753309
|Title=SOD2 gene polymorphisms in neovascular age-related macular degeneration and polypoidal choroidal vasculopathy
|OA=1
}}
{{PMID Auto
|PMID=19778569
|Title=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 Auto
|PMID=19863340
|Title=Influence of the polymorphism in candidate genes on late cardiac damage in patients treated due to acute leukemia in childhood
}}

{{PharmGKB
|RSID=rs4880
|Name_s=SOD1:Val16Ala
|Gene_s=SOD2
|Feature=
|Evidence=PubMed ID:19863340
|Annotation=Risk or phenotype-associated allele: C/T. Phenotype: There was no association between SOD1:Val16Ala and anthracycline induced cardiotoxicity. Study size: 76. Study population/ethnicity: Long-term survivals of pediatric acute lymphoblastic leukemia, Slovenia.
|Drugs=
|Drug Classes=ANTHRACYCLINES AND RELATED SUBSTANCES
|Diseases=Cardiomyopathies; Drug Toxicity; Heart Failure; Precursor Cell Lymphoblastic Leukemia-Lymphoma
|Curation Level=Curated
|PharmGKB Accession ID=PA165291871
}}
{{PMID Auto
|PMID=20043000
|Title=Association of SOD2, a Mitochondrial Antioxidant Enzyme, with Gray Matter Volume Shrinkage in Alcoholics
|OA=1
}}

{{PMID Auto
|PMID=20082738
|Title=Inter-individual variation in DNA damage and base excision repair in young, healthy non-smokers: effects of dietary supplementation and genotype
}}

{{PMID Auto
|PMID=20534900
|Title=SOD2 V16A SNP in the mitochondrial targeting sequence is associated with noise induced hearing loss in Chinese workers
|OA=1
}}
{{PMID Auto
|PMID=20378690
|Title=Genetic variants in selenoprotein genes increase risk of colorectal cancer
}}

{{PharmGKB
|RSID=rs4880
|Name_s=SOD2: Val16Ala; V16A; 47T>C; T47C; 47C-T; Ala16Val
|Gene_s=SOD2
|Feature=
|Evidence=PubMed ID:19509150
|Annotation=This variant is significantly associated with breast cancer outcome in breast cancer patients receiving cyclophosphamide-containing chemotherapy. Carriers of the Ala allele had inferior survival rates in the multivariate analysis.
|Drugs=cyclophosphamide
|Drug Classes=
|Diseases=Breast Neoplasms
|Curation Level=Curated
|PharmGKB Accession ID=PA164891515
}}

{{PharmGKB
|RSID=rs4880
|Name_s=SOD2: Val16Ala; V16A; 47T>C; T47C; 47C-T; Ala16Val
|Gene_s=SOD2
|Feature=
|Evidence=PubMed ID:12624725; PubMed ID:17192491
|Annotation=The VV genotype of rs4880 is significantly associated with an increased risk of diabetic nephropathy.
|Drugs=
|Drug Classes=
|Diseases=Diabetic Nephropathies
|Curation Level=Curated
|PharmGKB Accession ID=PA164891516
}}

{{PharmGKB
|RSID=rs4880
|Name_s=SOD2: Val16Ala; V16A; 47T>C; T47C; 47C-T; Ala16Val
|Gene_s=SOD2
|Feature=
|Evidence=PubMed ID:10425186; PubMed ID:15591282
|Annotation=The VV genotype of rs4880 is significantly associated with an increased risk of cardiomyopathy.
|Drugs=
|Drug Classes=
|Diseases=Cardiomyopathies; Cardiomyopathy, Dilated
|Curation Level=Curated
|PharmGKB Accession ID=PA164891517
}}

{{PharmGKB
|RSID=rs4880
|Name_s=SOD2: Val16Ala; V16A; 47T>C; T47C; 47C-T; Ala16Val
|Gene_s=SOD2
|Feature=
|Evidence=PubMed ID:10425186; PubMed ID:12618592; PubMed ID:15864132; PubMed ID:8633092
|Annotation=The variant protein carrying val16 allele has 30 to 40% lower activity and increases susceptibility to oxidative stress. The val16 allele disrupts the mitochondrial target sequence structure of SOD2 and causes the protein to be retained at the mitochondrial inner membrane whereas the Ala variant localizes to the mitochondrial matrix.
|Drugs=
|Drug Classes=
|Diseases=
|Curation Level=Curated
|PharmGKB Accession ID=PA164891518
}}
{{PMID Auto
|PMID=21062213
|Title=Manganese superoxide dismutase dimorphism relationship with severity and prognosis in cardiogenic shock due to dilated cardiomyopathy
}}

{{omim
|id=147460
|rsnum=4880
|variant=0001
}}

{{PMID Auto
|PMID=21567099
|Title=Estrogen metabolism genotypes, use of long-term hormone replacement therapy and risk of postmenopausal breast cancer
}}

{{PMID Auto
|PMID=21795425
|Title=Genetic Variation in Myeloperoxidase Modifies the Association of Serum {alpha}-Tocopherol with Aggressive Prostate Cancer among Current Smokers
|OA=1
}}

{{PMID Auto
|PMID=21915362
|Title=Sequence variants in antioxidant defense and DNA repair genes, dietary antioxidants, and pancreatic cancer risk
|OA=1
}}

{{PMID Auto
|PMID=22144047
|Title=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
|OA=1
}}

{{PMID Auto
|PMID=22206979
|Title=Genetic variants in antioxidant genes are associated with sperm DNA damage and risk of male infertility in a Chinese population
}}

{{PMID Auto
|PMID=21338322
|Title=Parameters of oxidative stress, DNA damage and DNA repair in type 1 and type 2 diabetes mellitus
}}

{{PMID Auto
|PMID=21351093
|Title=Association of superoxide dismutases and NAD(P)H quinone oxidoreductases with prognosis of patients with breast carcinomas
}}

{{ClinVar
|rsid=4880
|Reversed=1
|FwdREF=T
|FwdALT=C
|REF=A
|ALT=G
|RSPOS=160113872
|CHROM=6
|GMAF=0.3709
|dbSNPBuildID=52
|SSR=0
|SAO=1
|VP=0x05016800000015051f110100
|GENEINFO=SOD2:6648
|GENE_NAME=SOD2
|GENE_ID=6648
|WGT=0
|VC=SNV
|CLNALLE=1
|CLNHGVS=NC_000006.11:g.160113872A>G
|CLNSRC=OMIM Allelic Variant
|CLNORIGIN=1
|CLNSRCID=147460.0001
|CLNSIG=255
|CLNCUI=CN031984
|CLNDBN=SUPEROXIDE DISMUTASE 2 POLYMORPHISM; Microvascular complications of diabetes 6
|Disease=SUPEROXIDE DISMUTASE 2 POLYMORPHISM; Microvascular complications of diabetes 6
|CLNACC=RCV000015872.1; RCV000015873.1
|Tags=RV;PM;PMC;SLO;VLD;G5;HD;GNO;KGPhase1;KGPilot123;KGPROD;OTHERKG;PH3;LSD;OM
|CAF=0.6295; 0.3705
|CLNDSDB=MedGen:OMIM
|CLNDSDBID=CN031984:612634
|COMMON=1
}}

{{PMID Auto
|PMID=16385446
|Title=A testing framework for identifying susceptibility genes in the presence of epistasis.
|OA=1
}}

{{PMID Auto
|PMID=16543247
|Title=Polymorphisms in oxidative stress genes and risk for non-Hodgkin lymphoma.
}}

{{PMID Auto
|PMID=16945136
|Title=Gene x Gene interaction between MnSOD and GPX-1 and breast cancer risk: a nested case-control study.
|OA=1
}}

{{PMID Auto
|PMID=17293864
|Title=A common coding variant in CASP8 is associated with breast cancer risk.
}}

{{PMID Auto
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|Title=A genetic association analysis of cognitive ability and cognitive ageing using 325 markers for 109 genes associated with oxidative stress or cognition.
|OA=1
}}

{{PMID Auto
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|Title=Genetic association of glutathione peroxidase-1 with coronary artery calcification in type 2 diabetes: a case control study with multi-slice computed tomography.
|OA=1
}}

{{PMID Auto
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|Title=Correlating observed odds ratios from lung cancer case-control studies to SNP functional scores predicted by bioinformatic tools.
|OA=1
}}

{{PMID Auto
|PMID=18212354
|Title=Genes in glucose metabolism and association with spina bifida.
|OA=1
}}

{{PMID Auto
|PMID=18340529
|Title=A prospective study of genetic polymorphism in MPO, antioxidant status, and breast cancer risk.
|OA=1
}}

{{PMID Auto
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|Title=Gene polymorphisms of superoxide dismutases and catalase in diabetes mellitus.
|OA=1
}}

{{PMID Auto
|PMID=18676870
|Title=Variants in inflammation genes and the risk of biliary tract cancers and stones: a population-based study in China.
|OA=1
}}

{{PMID Auto
|PMID=18698231
|Title=Polymorphisms affecting gene transcription and mRNA processing in pharmacogenetic candidate genes: detection through allelic expression imbalance in human target tissues.
|OA=1
}}

{{PMID Auto
|PMID=18704161
|Title=Genetic variation in an individual human exome.
|OA=1
}}

{{PMID Auto
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|Title=Genetic underpinnings of tardive dyskinesia: passing the baton to pharmacogenetics.
}}

{{PMID Auto
|PMID=19074884
|Title=Interaction between single nucleotide polymorphisms in selenoprotein P and mitochondrial superoxide dismutase determines prostate cancer risk.
|OA=1
}}

{{PMID Auto
|PMID=19428448
|Title=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.
|OA=1
}}

{{PMID Auto
|PMID=19505917
|Title=Lead exposure, polymorphisms in genes related to oxidative stress, and risk of adult brain tumors.
|OA=1
}}

{{PMID Auto
|PMID=19754948
|Title=Evaluation of nine candidate genes in patients with normal tension glaucoma: a case control study.
|OA=1
}}

{{PMID Auto
|PMID=19946932
|Title=Lack of association of GPX1 and MnSOD genes with symptom severity and response to clozapine treatment in schizophrenia subjects.
}}

{{PMID Auto
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|Title=Gene polymorphisms against DNA damage induced by hydrogen peroxide in leukocytes of healthy humans through comet assay: a quasi-experimental study.
|OA=1
}}

{{PMID Auto
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|Title=Genetic Polymorphisms in Genes Related to Oxidative Stress (GSTP1, GSTM1, GSTT1, CAT, MnSOD, MPO, eNOS) and Survival of Rectal Cancer Patients after Radiotherapy.
|OA=1
}}

{{PMID Auto
|PMID=20477822
|Title=Single-nucleotide polymorphisms within the antioxidant defence system and associations with aggressive prostate cancer.
|OA=1
}}

{{PMID Auto
|PMID=20644561
|Title=A large-scale candidate gene approach identifies SNPs in SOD2 and IL13 as predictive markers of response to preoperative chemoradiation in rectal cancer.
}}

{{PMID Auto
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|Title=Association between the rs4880 superoxide dismutase 2 (C>T) gene variant and coronary heart disease in diabetes mellitus.
}}

{{PMID Auto
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|Title=Mn-SOD and CuZn-SOD polymorphisms and interactions with risk factors in gastric cancer.
|OA=1
}}

{{PMID Auto
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|Title=Superoxide dismutase and nicotinamide adenine dinucleotide phosphate: quinone oxidoreductase polymorphisms and pancreatic cancer risk.
}}

{{PMID Auto
|PMID=21181397
|Title=Association of the C47T polymorphism in SOD2 with diabetes mellitus and diabetic microvascular complications: a meta-analysis.
}}

{{PMID Auto
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|Title=Evaluation of the association studies of single nucleotide polymorphisms and hepatocellular carcinoma: a systematic review.
}}

{{PMID Auto
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|Title=Genetic polymorphisms in antioxidative enzymes are associated to forced expiratory volume in 1 s (FEV1) in smokers independently of asthma.
}}

{{PMID Auto
|PMID=21741706
|Title=Correlation of CYP2B6, CYP2C19, ABCC4 and SOD2 genotype with outcomes in allogeneic blood and marrow transplant patients.
}}

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|Title=The SOD2 C47T polymorphism influences NAFLD fibrosis severity: evidence from case-control and intra-familial allele association studies.
}}

{{PMID Auto
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|Title=PM10-induced hospital admissions for asthma and chronic obstructive pulmonary disease: the modifying effect of individual characteristics.
}}

{{PMID Auto
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|Title=Heterocyclic Aromatic Amine [HCA] Intake and Prostate Cancer Risk: Effect Modification by Genetic Variants.
}}

{{PMID Auto
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|Title=Genetic polymorphisms of antioxidant enzymes as risk factors for oxidative stress-associated complications in preterm infants.
}}

{{PMID Auto
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|Title=Antioxidant enzyme polymorphisms and neuropsychological outcomes in medulloblastoma survivors: a report from the Childhood Cancer Survivor Study.
|OA=1
}}

{{PMID Auto
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|Title=Candidate gene-based association study of antipsychotic-induced movement disorders in long-stay psychiatric patients: a prospective study
|OA=1
}}

{{GET Evidence
|gene=SOD2
|aa_change=Val16Ala
|aa_change_short=V16A
|impact=pharmacogenetic
|qualified_impact=Insufficiently evaluated pharmacogenetic
|inheritance=unknown
|quality_scores=Array
|dbsnp_id=rs4880
|overall_frequency_n=5122
|overall_frequency_d=10756
|overall_frequency=0.476199
|n_genomes=37
|n_genomes_annotated=0
|n_haplomes=48
|n_articles=5
|n_articles_annotated=5
|in_pharmgkb=Y
|nblosum100=2
|autoscore=1
|webscore=N
}}

{{PMID Auto
|PMID=23142385
|Title=Frequency of sepsis in patients with the 47C allele of SOD2 gene
}}

{{PMID Auto
|PMID=23500038
|Title=A Functional and Genetic Analysis of SOD2 Promoter Variants and their Contribution to Age-Related Hearing Loss
}}

{{PMID Auto
|PMID=23647424
|Title=Association of Mn-SOD Mutation (c.47T &gt; C) with Various POAG Clinical Indices
}}

{{PMID Auto
|PMID=24070129
|Title=Association of SOD2 Mutation (c.47T&#92;gtC) with Various Primary Angle Closure Glaucoma Clinical Indices
}}

{{PMID Auto
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|Title=Correlation between superoxide dismutase 1 and 2 polymorphisms and susceptibility to oral squamous cell carcinoma
|OA=1
}}

{{PMID Auto
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|Title=SOD2 gene Val16Ala polymorphism is associated with macroalbuminuria in Mexican type 2 diabetes patients: a comparative study and meta-analysis
|OA=1
}}

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}}

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|OA=1
}}

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|Title=Associations Between SNPs Within Antioxidant Genes and the Risk of Prostate Cancer in the Siberian Region of Russia
}}

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}}

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|OA=1
}}

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|Title=Genetic polymorphisms of antioxidant enzymes in preterm infants.
}}

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|Title=Aromatic DNA adducts and number of lung cancer risk alleles in Map-Ta-Phut Industrial Estate workers and nearby residents.
}}

{{PMID Auto
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|Title=Variation in PAH-related DNA adduct levels among non-smokers: the role of multiple genetic polymorphisms and nucleotide excision repair phenotype.
}}

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|Title=Influence of genetic polymorphisms on the association between phthalate exposure and pulmonary function in the elderly.
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}}
{{on chip | 23andMe v1}}
{{on chip | 23andMe v2}}
{{on chip | 23andMe v3}}
{{on chip | 23andMe v4}}
{{on chip | FTDNA2}}
{{on chip | HumanOmni1Quad}}
{{on chip | Illumina Human 1M}}