原创力文档a common complement c3 variant is associated with protection against wet age-related macular degeneration in a japanese population常见的补体c3变体与防止湿在日本人口年龄相关性黄斑变性.pdfVIP
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a common complement c3 variant is associated with protection against wet age-related macular degeneration in a japanese population常见的补体c3变体与防止湿在日本人口年龄相关性黄斑变性
A Common Complement C3 Variant Is Associated with
Protection against Wet Age-Related Macular
Degeneration in a Japanese Population
Suiho Yanagisawa, Naoshi Kondo*, Akiko Miki, Wataru Matsumiya, Sentaro Kusuhara, Yasutomo
Tsukahara, Shigeru Honda, Akira Negi
Department of Surgery, Division of Ophthalmology, Kobe University Graduate School of Medicine, Kobe, Japan
Abstract
Background: Genetic variants in the complement component 3 gene (C3) have been shown to be associated with age-
related macular degeneration (AMD) in Caucasian populations of European descent. In particular, a nonsynonymous coding
variant, rs2230199 (R102G), is presumed to be the most likely causal variant in the C3 locus based on strong statistical
evidence for disease association and mechanistic functional evidence. However, the risk allele is absent or rare (,1%) in
Japanese and Chinese populations, and the association of R102G with AMD has not been reported in Asian populations.
Genetic heterogeneity of disease-associated variants among different ethnicities is common in complex diseases. Here, we
sought to examine whether other common variants in C3 are associated with wet AMD, a common advanced-stage
manifestation of AMD, in a Japanese population.
Methodology/Principal Findings: We genotyped 13 tag single nucleotide polymorphisms (SNPs) that capture the majority
of common variations in the C3 locus and tested for associations between these SNPs and wet AMD in a Japanese
population comprising 420 case subjects and 197 controls. A noncoding variant in C3 (rs2241394) exhibited statistically
significant evidence of association (allelic P = 8.32 61024; odds ratio = 0.48 [95% CI = 0.31–0.74] for the rs2241394 C allele).
Multilocus logistic regression analysis confirmed that the effect of rs2241394 was independent of the previously described
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