Genetic aociation of manganee uperoxide dimutae with exudative age-related macular degeneration

PURPOE: To elucidate whether any polymorphic gene for xenobiotic-metabolizing and antioxidant enzyme are aociated with the development of exudative age-related macular degeneration. METHOD: A hopital-baed cae-control tudy wa performed on a conecutive erie of 102 Japanee patient with the exudative form of age-related macular degeneration who were recruited between 1993 and 1998 in the Kagohima Univerity Hopital. Control were 200 ytemically healthy individual who had no enecent ocular diorder and were over 50 year of age. There wa no evidence of age-related macular degeneration in the 200 control. Genomic DNA from peripheral blood wa examined uing polymerae chain reaction and defined for the genetic polymorphim of cytochrome P-450 1A1, glutathione -tranferae, microomal epoxide hydrolae, and manganee uperoxide dimutae. REULT: We found a ignificant aociation of manganee uperoxide dimutae gene polymorphim, valine/alanine polymorphim at the targeting equence of the enzyme, with age-related macular degeneration. The patient had an increaed frequency of alanine allele and alanine/alanine genotype (odd RATIO = 10.14, 95% confidence INTERVAL = 4.84 to 2.13; P = .0005 after Bonferroni correction). We alo oberved a weak aociation of microomal epoxide hydrolae exon-3 polymorphim with age-related macular degeneration (odd RATIO = 2.20, 95% confidence INTERVAL = 4.02 to 1.20; P = .020 after Bonferroni correction). Cytochrome P-450 1A1, glutathione -tranferae, and microomal epoxide hydrolae exon-4 were polymorphic, but their genotype frequency ditribution did not how a tatitically ignificant difference between the patient and control. CONCLUION: The reult ugget that manganee uperoxide dimutae gene polymorphim i aociated with exudative age-related macular degeneration. Microomal epoxide hydrolae i another enzyme that may be aociated with the dieae. The exudative form of age-related macular degeneration may have genetic rik factor againt oxidative tre and/or effect of xenobiotic. Further aociation tudie in other polymorphic gene for xenobiotic-metabolizing enzyme are needed to elucidate the environmental–genetic interaction in the underlying caue of age-related macular degeneration.