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Abstract

We appreciate Gotoh and associates' critical reading of our article reporting an association of manganese superoxide dismutase (SOD2) gene polymorphism with exudative age-related macular degeneration (AMD). 1 Kimura K. Isashiki Y. Sonoda S. Kakiuchi-Matsumoto T. Ohba N. Genetic association of manganese superoxide dismutase with exudative age-related macular degeneration. Am J Ophthalmol. 2000; 130: 769-773 Abstract Full Text Full Text PDF PubMed Scopus (119) Google Scholar Their failure to replicate our results remains to be elucidated. A polymerase chain reaction–restriction determination of the SOD2 allele used in our study has been proved valid elsewhere, 2 Nakao K. Isashiki Y. Sonoda S. Uchino E. Shimonagano Y. Sakamoto T. Nitric oxide synthase and superoxide dismutase gene polymorphisms in Behçet disease. Arch Ophthalmol. 2007; 125: 246-251 Crossref PubMed Scopus (21) Google Scholar and there is noticeably no substantial difference in the SOD2 allelic distribution between their control subjects and ours. One possible explanation to be examined to determine the discrepancy between Gotoh and associates' and our observations is the differences in the genetic or anthropologic background of the sample population, that is, AMD patients in the southern region of Japan and those in the central region. Our analysis in terms of the mitochondrial D-loop haplotype suggests that approximately half of our sample population from Southern Japan is assigned to the phylogenetic cluster that is dominant for Okinawa or Thailand, but not for the central Japan. 3 Isashiki Y. Sonoda S. Izumo S. Sakamoto T. Tachikui H. Inoue I. Phylogenetic assessment of the mitochondrial DNA displacement loop haplotype in Japanese patients with Leber's hereditary optic neuropathy harboring the mitochondrial DNA G11778A mutation. Ophthalmic Res. 2003; 35: 224-231 Crossref PubMed Scopus (9) Google Scholar The SOD2 molecule may play a crucial role in the protection of the retinal pigment epithelium (RPE) against oxidative stress that has been thought to be one of the major factors involved in RPE cell death in AMD. 4 Kasahara E. Lin L.-R. Ho Y.-S. Reddy V.N. SOD2 protects against oxidation-induced apoptosis in mouse retinal pigment epithelium: implications for age-related macular degeneration. Invest Ophthalmol Vis Sci. 2005; 46: 3426-3434 Crossref PubMed Scopus (84) Google Scholar Therefore, it is justified to repeat studies to define further a possible molecular association with disease susceptibility in a larger number of samples with haplotype analysis of intragenic polymorphisms in a single gene. 5 Esfandiary H. Chakravarthy U. Patterson C. Young I. Hughes A.E. Association study of detoxification genes in age-related macular degeneration. Br J Ophthalmol. 2005; 89: 470-474 Crossref PubMed Scopus (56) Google Scholar Manganese Superoxide Dismutase Gene (SOD2) Polymorphism and Exudative Age-related Macular Degeneration in the Japanese PopulationAmerican Journal of OphthalmologyVol. 146Issue 1PreviewThe article by Kimura and associates demonstrated that the manganese superoxide dismutase gene (SOD2) polymorphism, the C allele of rs4880, conferred the risk for exudative age-related macular degeneration (AMD) in the Japanese population.1 Doubts regarding this variant as a risk factor for exudative AMD had been raised by a previous study of Esfandiary and associates with a study sample from Northern Ireland.2 We attempted to replicate the study using a larger cohort that harbored the same genetic background as was seen in the original study that demonstrated positive results. Full-Text PDF