Wang Zilin, Zou Minjie, Chen Aiming, Liu Zhenzhen, Young Charlotte Aimee, Wang Shi-Bin, Zheng Danying, Jin Guangming
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, China.
Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
Acta Ophthalmol. 2022 May;100(3):e669-e680. doi: 10.1111/aos.14970. Epub 2021 Aug 17.
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).
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.
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.
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.
研究所有已报道的常见多态性与抗血管内皮生长因子（VEGF）治疗反应之间的关联，并确定年龄相关性黄斑变性（AMD）患者抗VEGF治疗反应的潜在临床有用生物标志物。
我们检索了英文的Embase、PubMed、Web of Science数据库以及中文的中国知网、万方和维普数据库，以查找关于AMD患者抗VEGF治疗反应的药物遗传学研究。使用随机效应模型计算比值比及其95%置信区间。
在文献检索得到的10468条记录中，33篇符合纳入标准的文章被纳入荟萃分析。观察到四个基因中的九个单核苷酸多态性（SNP）与AMD患者的抗VEGF治疗反应相关。即，HTRA1基因中的rs1120063；年龄相关性黄斑病变易感性（ARMS2）基因中的rs10490924；补体因子H（CFH）基因中的rs1061170；以及OR52B4基因中的rs323085与良好的抗VEGF治疗反应相关，而CFH基因中的rs800292、rs1410996和rs1329428以及OR52B4基因中的rs4910623和rs10158937与我们样本中AMD患者的抗VEGF治疗反应不佳相关。
在本研究中，四个基因的九个SNP被表明与样本中的抗VEGF治疗反应显著相关：HTRA1基因中的rs11200638；ARMS2基因中的rs10490924；CFH基因中的rs1061170、rs800292、rs1410996和rs1329428；以及OR52B4基因中的rs323085、rs4910623和rs10158937。有必要基于不同种族和大样本量进行进一步研究，以加强本研究中发现的证据。
