Genetic association of manganese superoxide dismutase with exudative age-related macular degeneration

PURPOSE: To elucidate whether any polymorphic genes for xenobiotic-metaboli zing and antioxidant enzymes are associated with the development of exudati ve age-related macular degeneration. METHODS: A hospital-based case-control study was performed on a consecutive series of 102 Japanese patients with the exudative form of age-related mac ular degeneration who were recruited between 1993 and 1998 in the Kagoshima University Hospital. Controls were 200 systemically healthy individuals wh o had no senescent ocular disorders and were over 50 years of age. There wa s no evidence of age-related macular degeneration in the 200 controls, Geno mic DNA from peripheral bloods was examined using polymerase chain reaction and defined for the genetic polymorphisms of cytochrome P-450 1A1, glutath ione S-transferases, microsomal epoxide hydrolase, and manganese superoxide dismutase. RESULTS: We found a significant association of manganese superoxide dismuta se gene polymorphism, valine/alanine polymorphism at the targeting sequence of the enzyme, with age-related macular degeneration, The patients had an increased frequency of alanine allele and alanine/alanine genotype (odds ra tio = 10.14, 95% confidence interval = 4.84 to 2.13; P = .0005 after Bonfer roni correction). We also observed a weak association of microsomal epoxide hydrolase exon-3 polymorphism with age related macular degeneration (odds ratio = 2.20, 95% confidence interval = 4.02 to 1.20; P = .020 after Bonfer roni correction). Cytochrome F-450 1A1, glutathione S-transferases, and mic rosomal epoxide hydrolase exon 4 were polymorphic, but their genotype frequ ency distributions did not show a statistically significant difference betw een the patients and controls. CONCLUSIONS: The results suggest that manganese superoxide dismutase gene p olymorphism is associated with exudative age-related macular degeneration. Microsomal epoxide hydrolase is another enzyme that may be associated with the disease. The exudative form of age related macular degeneration may hav e genetic risk factors against oxidative stress and/or effects of xenobioti cs, Further association studies in other polymorphic genes for xenobiotic-m etabolizing enzymes are needed to elucidate the environmental-genetic inter action in the underlying cause of age-related macular degeneration. (C) 200 0 by Elsevier Science Inc. All rights reserved.