The Investigation Of The Genetic Effect On The Non-response To The Anti-angiogenesis Treatment Of Exclusive Age-related Macular Degeneration

Objective: To assess the association between HTRA1 gene rs11200638 G→A polymorphism and anti-angiogenesis treatment response to exudative AMD using the meta-analysis method.Methods: We electronically searched PubMed,Embase and Cochrane Library databases,screened the cohort studies including neovascular AMD and polypoidal choroidal vasculopathy(PCV)patients.Treatments included anti-VEGF(bevacizumab or ranibizumab)or/and photodynamic therapy.Summary odds ratios(ORs)of the responders and non-reaponders and 95% confidence intervals(CIs)were estimated by applying both fixed-and random-effects models in Review Manager 5.3.Q-statistic test was used to assess heterogeneity.The Newcastle-Ottawa Scale(NOS)for assessing the quality of the studies.Results: 9 published associated studies containing 2096 patients were included.Polymorphism rs11200638 in HTRA1 gene showed a significant summary ORs in the overall population for the response to anti-angiogenesis treatment in exudative AMD(GG+GA versus AA: OR 1.56(95% CI 1.10 to 2.20),p=0.04,random model).In subgroup analysis,rs11200638 appeared more likely to be a predictor for antiangiogenic response in the East Asian population(GG versus AA: OR 1.94(95% CI 1.19 to 3.16),p=0.08,fix model;GA versus AA: OR 1.47(95% CI 1.04 to 2.09),p=0.03,fix model;GG+GA versus AA: OR 1.57(95% CI 1.13 to 2.17),p=0.007,fix model;G versus A: OR 1.47(95% CI 1.15 to 1.86),P=0.002,fix model.);For the East Asian individuals with PCV group,they acquired larger ORs(GG vs AA: OR 3.58(95% CI 1.31 to 9.83),p=0.01,fix model;GA vs AA: OR 1.80(95% CI 0.86 to 3.75),p=0.12,fix model;GG+GA vs AA: OR 2.14(95% CI 1.07 to 4.27),p=0.03,fix model;G vs A: OR 1.86(95% CI 1.16 to 2.98),P=0.01,fix model;)than without PCV group(GG versus AA: OR 1.55,95% CI 0.87-2.74,fix model;GA versus AA: OR 1.65,95%CI: 0.64-4.25,random model;GG+GA versus AA: OR 1.63 95%CI: 0.75-3.53,random model;G versus A: OR 1.34,95%CI: 1.01-1.78,fix model.).However,no statistical significance was found in the Caucasian subgroup analysis.Conclusions: HTRA1 rs11200638 might be associated with the anti-angiogenesis treatment response to exudative AMD for the East Asian population,especially for individuals with PCV group,patients with risk allele A acquire a poor response.It might be the genetic biomarker spectrum to allow treatment individualization though a further validation,and larger sample size studies are needed.