The Association Between Complement Component 2/Complement Factor B Polymorphisms and Age-related Macular Degeneration: A HuGE Review and Meta-Analysis

Abstract

The authors performed a systematic review of the association of complement component 2(C2)/complement factor B (CFB) gene polymorphisms with age-related macular degeneration (AMD). In total, data from 19 studies published between 2006 and 2011 were pooled for 4 polymorphisms: rs9332739 and rs547154 in the C2 gene and rs4151667 and rs641153 in the CFB gene. Data extraction and assessments for risk of bias were independently performed by 2 reviewers. Allele frequencies and allele and genotypic effects were pooled. Heterogeneity and publication bias were explored. Pooled minor allele frequencies for all 4 SNPs were between 4.7% and 9.6% for all polymorphisms, except for an Indian population in which the C allele at rs9332739 was the major allele. For the C2 polymorphisms, the minor C allele at rs9332739 and the minor T allele at rs547154 carried estimated relative risks (odds ratios) of 0.55 (95% confidence interval (CI): 0.46, 0.65) and 0.47 (95% CI: 0.39, 0.57), respectively. For the CFB polymorphisms, the minor A alleles at rs4151667 and rs614153 carried estimated risks of 0.54 (95% CI: 0.45, 0.64) and 0.41 (95% CI: 0.34, 0.51), respectively. These allele effects contributed to an absolute lowering of the risk of all AMD in Caucasian populations by 2.0%-6.0%. This meta-analysis provides a robust estimate of the protective association of C2/CFB with AMD.

Age-Related Macular Degeneration: A Complementopathy?

“…Various polymorphisms in a gene region encoding FB and C2 have been shown to be associated with AMD [55]. It is probable that several of the single-nucleotide polymorphisms tested are in strong linkage disequilibrium with a variant of FB (R32Q).…”

Bowman lecture on the role of inflammation in degenerative disease of the eye

“…The inclusion of AMD in this set of conditions has arisen because of the suggestion that complement may have a role in AMD, based on the altered susceptibility risk to carriers of mutations in certain genes such as complement factors H and B. 54,55 Several other genetic links to AMD have since been identified although not with such strong associations. 56 In the initial rush to provide a mechanism, it was proposed that defects in complement activation were related to the ingress of pathogenic inflammatory cells, which had been identified as part of the pathology of AMD by Penfold et al 57,58 in the early 1980s.…”

Complement Factor B Polymorphism and the Phenotype of Early Age-related Macular Degeneration

“…[13][14][15] Similarly, the influence of the CFB and C2 haplotype has been shown in various populations. [16][17][18][19][20][21][22][23][24] The clinical features of AMD vary markedly among individuals. However, twin and sibling studies have provided substantial evidence of the genetic effect on the phenotype.…”