LOC387715/HTRA1 gene polymorphisms and susceptibility to age-related macular degeneration: A HuGE review and meta-analysis

PURPOSE: To examine the association of age-related macular degeneration (AMD) with HtrA serine peptidase 1 (HTRA1) gene rs11200638 G→A polymorphism and LOC387715/ ARMS2 gene rs10490924 G→T polymorphisms, and to evaluate the magnitude of the gene effect and the possible genetic mode of action. METHODS: We searched the US National Library of Medicine’s PubMed, Embase, OMIM, ISI Web of Science, and CNKI databases in a systematic manner to retrieve all genetic association studies on the HTRA1 (rs11200638) and LOC387715/ ARMS2 (rs10490924) gene polymorphisms and AMD. We performed a meta-analysis conducted with Stata software, version 9.0. RESULTS: Individuals who carried the AA and AG genotypes of HTRA1 gene rs11200638 G→A polymorphism had 2.243 and 8.669 times the risk of developing AMD, respectively, when compared with those who carry the GG genotype. Individuals carrying the TT and TG genotypes of LOC387715/ ARMS2 gene rs10490924 G→T polymorphism had 7.512 and 2.353 times the risk of developing AMD, respectively, compared with those who carry GG genotype. These results suggested a “moderate” codominant, multiplicative genetic mode; that is, both HTRA1 rs11200638 G→A polymorphism and LOC387715/ARMS2 rs10490924 G→T polymorphism play important roles in the pathogenesis of AMD. We found no evidence of publication bias. Between-study heterogeneity was found in both allele-based analysis and genotype-based analysis. CONCLUSIONS: HTRA1 rs11200638 G→A polymorphism and LOC387715/ARMS2 rs10490924 G→T polymorphism play important roles in AMD. Gene-gene and gene-environmental interactions, as well as precise mechanisms underlying common variants in the HTRA1 gene and LOC387715/ ARMS2 gene, potentially increase the risk of AMD and need further exploration.