rs4880

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 , 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 . 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. * 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. * 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). * 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). * 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. * 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. ** 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 ** A 2014 Danish meta-analysis plus study of ~300 patients receiving cyclophosphamide chemotherapy found no association with rs4880(C) genotype ** 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 * See also OMIM 147460.0001 * Note: rs1799725 was combined into rs4880 by dbSNP The C allele of rs4880 appears to be slightly associated with Alzheimer's disease. rs2758346 rs4880 and rs2855116 association with Alzheimer's disease {{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 }}