HTRA1 Promoter Polymorphism and Risk of Age-Related Macular Degeneration: A Meta-Analysis

PurposeTo clarify the role of human high-temperature requirement A-1 (HTRA1) gene promoter polymorphism (-512G>A) in age-related macular degeneration (AMD).MethodsRelevant studies were identified by searching PubMed and EMBASE database. A logistic regression analysis proposed for molecular association studies was carried out to estimate the genetic effect and the possible genetic model of action.ResultsFourteen case-control studies were included in this meta-analysis. There was strong evidence for an association between HTRA1 -512G>A polymorphism and AMD (p < 0.001). The genetic model test indicated that the genetic model was most likely to be co-dominant. Overall, our meta-analysis showed that AA and GA genotypes were associated with increased risk of AMD (AA vs. GG: odds ratio1 [OR1] = 7.46; 95% confidence interval [CI] = 6.16-9.04; GA vs. GG: OR2 = 2.27, 95% CI = 2.02–2.55). In stratified analysis by ethnicity and age, the genetic effect seemed to be stronger in Caucasians and subjects ≥73 years of age than in Asians and subjects <73 years of age. When subgroup analysis was conducted by AMD type, significant association was noted for wet AMD but not for dry AMD.ConclusionsThis meta-analysis summarizes the strong evidence for an association between HTRA1 -512G>A polymorphism and AMD and indicates a co-dominant model of action.