title: Systematic review and meta-analysis of the association between complement factor H Y402H polymorphisms and age-related macular degeneration.
abstract: Age-related macular degeneration (AMD) is the leading cause of blindness in the developed world and complement factor H (CFH) polymorphism has been found to associated with the AMD. We performed a meta-analysis to estimate the magnitude of the gene effect and the possible mode of action. A meta-analysis of eight studies assessing association between the CFH Y402H polymorphism and AMD was performed. Data extraction and study quality assessment were performed in duplicate, and heterogeneity and publication bias were explored. There was strong evidence for association between CFH and AMD, with those having CC and TC genotypes being roughly six and 2.5 times more likely to have AMD than patients with TT genotype, suggesting a co-dominant, multiplicative genetic model. The population attributable risk for the CC/TC genotype is 58.9%, i.e. the CFH polymorphism is involved in over half of all AMD. This meta-analysis summarizes the strong evidence for an association between CFH and AMD and indicates a multiplicative model with each C allele increasing the odds of AMD by approximately 2.5-fold. This result is at least as important at the population level as ApoE4 and Alzheimer's disease, playing a role in almost 60% of AMD at the population level.
authors.affiliation: Centre for Clinical Epidemiology and Biostatistics, School of Medical Practice and Population Health, University of Newcastle, NSW, Australia, and Clinical Epidemiology Unit, Ramathibodi Hospital, Bangkok, Thailand. ammarin.thakkinstian@newcastle.edu.au
authors.forename: Ammarin
authors.initials: A
authors.lastname: Thakkinstian
authors.forename: Pearline
authors.initials: P
authors.lastname: Han
authors.forename: Mark
authors.initials: M
authors.lastname: McEvoy
authors.forename: Wayne
authors.initials: W
authors.lastname: Smith
authors.forename: Josephine
authors.initials: J
authors.lastname: Hoh
authors.forename: Kristinn
authors.initials: K
authors.lastname: Magnusson
authors.forename: Kang
authors.initials: K
authors.lastname: Zhang
authors.forename: John
authors.initials: J
authors.lastname: Attia
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D019943:Amino Acid Substitution; D017242:Complement Factor H / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide
chemical_list: D017242:Complement Factor H