CFB/C2 gene polymorphisms and risk of age-related macular degeneration: A systematic review and meta-analysis

Abstract

Purpose: To investigate whether the polymorphisms of CFB/C2 gene are associated with age-related macular degeneration (AMD), and to evaluate the magnitude of gene effect. Methods: We performed a meta-analysis of the association between four SNPs in CFB/C2 gene (rs9332739, rs547154, rs4151667, and rs641153) and risk of AMD using data from 15 case-control studies involving 8905 subjects. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using fixed- and random-effects models. The Q and I 2 statistics were used to evaluate between-study heterogeneity. Harbord's modified test was used to detect small study effects. Sensitivity analysis, cumulative meta-analysis, and meta-regression were also performed. Results: For rs9332739, rs547154, rs4151667, and rs641153, the pooled ORs in a dominant genetic model were 0.474 (fixed effects, P<0.001, 95% CI 0.378-0.596), 0.399 (random effects, 95% CI 0.289-0.551, P<0.001), 0.496 (fixed effects, 95% CI 0.390-0.632, P<0.001), and 0.557 (random effects, P=0.008, 95% CI 0.362-0.856), respectively. These results suggested that variant alleles of all the four SNPs has significant protective effect against AMD. Contour-enhanced funnel plots and Harbord's test showed moderate small study effects for rs9332739 and rs4151667. Heterogeneity were found for rs547154 and rs641153, subgroup analysis suggested that ethnicity was the main source for heterogeneity. Stratification by ethnicity indicated stronger protective effects of rare alleles in Caucasians. Genotype distribution analysis also suggested that frequencies of rare homozygous genotype were higher in Caucasian group. Conclusions: Our meta-analysis indicated strong protective effects of the variant alleles of four SNPs in CFB/C2 gene (rs9332739, rs547154, rs4151667, and rs641153) against AMD. The disease risk descended to nearly one half for individuals carrying at least one copy of the rare alleles. The protective effects seemed to be stronger in Caucasians, of which the genotype frequencies were also higher. © 2012 Informa Healthcare USA, Inc.