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Isao Nakata, Kenji Yamashiro, Hideo Nakanishi, Hisako Hayashi, Yumiko Kurashige, Akitaka Tsujikawa, Atsushi Otani, Nagahisa Yoshimura; C2/CFB Gene Variants and Japanese Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5225.
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ARMS2/HTRA1 locus, complement factor H (CFH), and C2/complement factor B (CFB) locus are known to be 3 major age-related macular degeneration (AMD)-associated loci. However, no Asian report showed a positive association in C2/CFB gene for developing AMD. Furthermore, although a study in Caucasian showed a significant association between C2/CFB and developing polypoidal choroidal vasculopathy (PCV), no Asian report found a positive association. The purpose of this study is to investigate, in a Japanese population, whether or not genetic variants in C2/CFB locus are associated with the risk of developing typical AMD or PCV.
We performed a case-control study in a sample of Japanese patients with typical AMD (n = 455) or PCV (n = 581) and in 865 healthy Japanese individuals. Genotypes of C2 rs547154 and three single nucleotide polymorphisms (SNPs) across the CFB gene (rs541862, rs2072633 and rs4151672) were determined using the Taqman SNP assay. The diagnosis of PCV was based on indocyanine green angiography, which showed a branching vascular network terminating in polypoidal swelling. Information on the smoking status was obtained by self-reported questionnaire. The Hardy-Weinberg equilibrium (HWE) for the genotypic distribution was determined with the HWE-exact test for each group. Statistical analyses for differences in the observed genotypic distribution were performed by logistic regression analysis for age and gender adjustments. The level of statistical significance was set at P < 0.05.
The distributions of the genotypes for all study groups were in Hardy-Weinberg equilibrium (P > 0.05). C2 rs547154 and CFB rs541862 showed significant association with both typical AMD (P = 0.010 and 0.010, respectively) and PCV (P = 0.018 and 0.016, respectively). These two SNPs are in strong linkage disequilibrium (pair-wise D’ =1.0 and r2 = 1.0). Next, we conducted logistic regression analyses including the effects of the most robust Japanese AMD/PCV-associated variants, ARMS2 A69S (rs10490924) and CFH I62V (rs800292), as well as age, gender and smoking status in the regression model. C2/CFB rs547154 retained significant association for both typical AMD and PCV (P = 0.0073 and 0.0083, respectively) even after considering the effects of these covariates.
In the present study we were able to replicate the reported association between genetic variants in C2/CFB locus and both typical AMD and PCV in Japanese.
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