Association Between Complement Factor C2/C3/CFB/CFH Polymorphisms and Age-Related Macular Degeneration: A Meta-Analysis.

BACKGROUND:Several previous studies have assessed the contribution of polymorphisms in genes encoding the complement factors C2/C3/CFB/CFH with the risk of age-related macular degeneration (AMD), however the results have been inconsistent. We conducted a meta-analysis to systematically review the potential association between complement factor polymorphisms and AMD. METHODS:Studies that investigated associations between C2 (rs547154 and rs9332739), C3 (rs1047286), CFB (rs4151667 and rs641153), and CFH (rs551397 and rs2274700) polymorphisms and AMD were identified by searching PubMed, EMBASE, Web of Science, and Cochrane Library databases for articles published prior to January 1, 2018. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to evaluate the association between these polymorphisms and AMD using Stata 12.0 software. Q and I² statistics were used to evaluate between-study heterogeneity. Publication bias analyses were conducted using Begg's test. We also conducted an ethnic subgroup analysis. RESULTS:A total of 53 studies that included data for 53,774 patients and 56,973 healthy controls were evaluated. The pooled ORs for rs551397, rs2274700, rs4151667, rs641153, rs1047286, rs9332739, and rs547154 in the heterozygote model were 0.53 (95% CI: 0.45-0.61), 0.53 (95% CI: 0.40-0.70), 0.54 (95% CI: 0.46-0.63), 0.48 (95% CI: 0.4-0.57), 1.42 (95% CI: 1.22-1.66), 0.5 (95% CI: 0.45-0.56), and 0.52 (95% CI: 0.43-0.62), respectively. CONCLUSION:Our findings from this analysis confirmed the protective role of C2/CFB/CFH polymorphisms in the development of AMD, but showed that the single nucleotide polymorphism in C3 was a high-risk factor for AMD. The racial analysis results suggested that the effect of variant alleles was stronger in Caucasians than Asians.

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