Genetic associations of anti-vascular endothelial growth factor therapy response in age-related macular degeneration: a systematic review and meta-analysis

Purpose To investigate the association of all reported common polymorphisms in anti-vascular endothelial growth factor (VEGF) therapy response and to identify potential clinically useful biomarkers for anti-VEGF therapy response in patients with age-related macular degeneration (AMD). Methods We searched the Embase, PubMed, Web of Science databases in English and the China National Knowledge Infrastructure, WanFang and VIP databases in Chinese for pharmacogenetics studies on anti-VEGF therapy response in AMD. Odds ratios with 95% confidence intervals were calculated using the random effects model. Results Among the 10 468 records yielded by the literature search, 33 articles that met the eligibility criteria were included in the meta-analysis. Nine single-nucleotide polymorphisms (SNP) in four genes were observed to be associated with the anti-VEGF therapy response in AMD patients. That is, rs1120063 in the HTRA1 gene; rs10490924 in the age-related maculopathy susceptibility (ARMS2) gene; rs1061170 in the complement factor H (CFH) gene; and rs323085 in the OR52B4 gene were associated with good anti-VEGF therapy responses, while rs800292, rs1410996 and rs1329428 in the CFH gene and rs4910623 and rs10158937 in the OR52B4 gene were associated with poor anti-VEGF therapy response in the AMD patients in our sample. Conclusion In this study, nine SNPs of four genes were indicated to be significantly associated with the anti-VEGF therapy response in the samples: rs11200638 in the HTRA1 gene; rs10490924 in the ARMS2 gene; rs1061170, rs800292, rs1410996 and rs1329428 in the CFH gene; and rs323085, rs4910623 and rs10158937 in the OR52B4 gene. Further studies based on various ethnicities and large sample sizes are warranted to strengthen the evidence found in the present study.