Purpose: To determine the characteristics of the polymorphisms in the ARMS2 gene in Japanese patients with age-related macular degeneration (AMD) and those with polypoidal choroidal vasculopathy (PCV) and in healthy controls, and also to show possible associations of the polymorphisms with the disease.
Design: Case-control association study.
Methods: Fifty-six unrelated Japanese individuals with AMD, 55 with PCV, and 77 controls were studied. The most common polymorphism in the ARMS2 gene on chromosome 10 was resequenced. Association tests were performed for inferred haplotypes.
Results: A total of 22 polymorphisms were identified, and 13 were shared with those in White persons with AMD. The sequence of the deletion-and-insertion polymorphism, de1443ins54, a functional polymorphism causing an instability of the messenger ribonucleic acid of ARMS2 in the Japanese, did not differ from that in White persons. Among the polymorphisms seen in the White population, rs10490923 (R3H) as well as 7 other polymorphisms were not observed in the Japanese. One haplotype, which contained the T allele of the rs10490924 (A69S) and the variant of de1443ins54 polymorphism, had an odds ratio of 3.14 (P = 7.8 x 10(-6)) for AMD and 2.00 (P = .0058) for PCV. Among the 9 polymorphisms that were unique to the Japanese population, 2 had a minor allelic frequency of more than 0.05, and these 2 polymorphism were included as nonrisk haplotypes.
Conclusions: The de1443ins54 polymorphism is a common variant between White and Japanese populations. It is strongly associated not only with AMD but also with PCV.