Systematic review and meta-analysis of the association between complement component 3 and age-related macular degeneration: a HuGE review and meta-analysis

• Published in: American journal of epidemiology Vol. 173; no. 12; pp. 1365 - 1379
• Main Authors: Thakkinstian, Ammarin, McKay, Gareth J, McEvoy, Mark, Chakravarthy, Usha, Chakrabarti, Subhabrata, Silvestri, Giuliana, Kaur, Inderjeet, Li, Xiaoxin, Attia, John
• Format: Journal Article
• Language: English
• Published: United States Oxford Publishing Limited (England) 15.06.2011
• Subjects: Age Factors; Asian Continental Ancestry Group - genetics; Complement C3 - genetics; Ethnicity; European Continental Ancestry Group - genetics; Genetic Predisposition to Disease; Genetics; Genotype & phenotype; Humans; Macular degeneration; Macular Degeneration - ethnology; Macular Degeneration - genetics; Meta-analysis; Polymorphism; Systematic review
• ISSN: 0002-9262; 1476-6256
• DOI: 10.1093/aje/kwr025

The authors performed a meta-analysis to estimate the magnitude of polymorphism effects for the complement component C3 gene (C3) and their possible mode of action on age-related macular degeneration (AMD). The meta-analysis included 16 and 7 studies for rs2230199 and rs1047286, respectively. Data extraction and risk of bias assessments were performed in duplicate, and heterogeneity and publication bias were explored. There was moderate evidence for association between both polymorphisms and AMD in Caucasians. For rs2230199, patients with CG and GG genotypes were 1.44 (95% confidence interval (CI): 1.33, 1.56) and 1.88 (95% CI: 1.59, 2.23) times more likely to have AMD than patients with the CC genotype. For rs1047286, GA and AA genotypes had 1.27 (95% CI: 1.15, 1.41) and 1.70 (95% CI: 1.27, 2.11) times higher risk of AMD than did GG genotypes. These gene effects suggested an additive model. The population attributable risks for the GG/GC and AA/GA genotypes are approximately 5%-10%. Subgroup analysis by ethnicity indicates that these variants are very infrequent in Asians and that the observed gene effects are based largely on the high frequency within Caucasian populations. This meta-analysis supports the association between C3 and AMD and provides a robust estimate of the genetic risk.