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 study of 248 US and 340 Norwegian patients.


 * See also OMIM 147460.0001


 * Note: rs1799725 was combined into rs4880 by dbSNP

The C allele of rs4880 appears to be associated with Alzheimer's disease. rs2758346 rs4880 and rs2855116 association with Alzheimer's disease