Pharmacogenetic studies indicate that a variable response to anti-vascular endothelial growth factor (VEGF) therapy in patients with neovascular form of AMD (nAMD) may be due to polymorphisms in the complement factor H gene (CFH). This study is the first to investigate the association between CFH Y402H polymorphism and the response to ranibizumab therapy in Malaysian patients with nAMD. We included 134 patients with nAMD, examined between September 2014 and February 2016. The diagnosis of nAMD was confirmed by ophthalmologic examination, before ranibizumab therapy was started. Each patient received an intravitreal injection of 0.5 mg/0.05 ml ranibizumab following a treat-and-extend (TE) regimen. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were recorded after 3 and 6 months following the first injection and compared with the baseline values. Genotyping of Y402H (rs1061170) polymorphism was performed using PCR-RFLP and the amplified product was digested with MluCI restriction enzyme. Association between the Y402H genotypes and response to treatment was determined by a logistic regression analysis of responder (n = 49) and non-responder (n = 84) group. Significantly worse mean BCVA was observed for the CC genotype compared to the TT + CT genotype in the total sample after 6-month follow-up (p = 0.018). Comparing the baseline and 6-month point measurements, improved mean BCVA was observed in responder group, while worse mean BCVA was recorded for non-responder group. However, our regression analysis, adjusted for confounding factors, showed no significant association between the Y402H genotypes and response to treatment in nAMD patients under the recessive model (p > 0.05). Overall, our results suggest that factors other than Y402H polymorphism may be involved in the progression of nAMD after treatment with anti-VEGF agents, in Malaysian population.

中文翻译：

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新血管性年龄相关性黄斑变性（nAMD）患者CFH Y402H多态性与对玻璃体内兰尼单抗反应的相关性分析。

药物遗传学研究表明，新血管形式的AMD（nAMD）患者对抗血管内皮生长因子（VEGF）治疗的反应不同，可能是由于补体因子H基因（CFH）的多态性引起的。这项研究是首次调查CFH Y402H基因多态性与马来西亚nAMD患者对兰尼单抗治疗反应之间的关系。我们纳入了2014年9月至2016年2月之间检查的134例nAMD患者。在开始使用兰尼单抗治疗之前，已通过眼科检查确认了nAMD的诊断。在治疗和延长（TE）方案后，每位患者接受了0.5 mg / 0.05 ml雷珠单抗的玻璃体内注射。首次注射后3和6个月记录最佳矫正视力（BCVA）和视网膜中央厚度（CRT），并与基线值进行比较。使用PCR-RFLP对Y402H（rs1061170）多态性进行基因分型，并用MluCI限制酶消化扩增的产物。Y402H基因型与对治疗的反应之间的关联通过对反应者（n = 49）和无反应者（n = 84）组进行逻辑回归分析确定。随访6个月后，总样本中CC基因型的平均BCVA较TT + CT基因型差得多（p = 0.018）。比较基线和6个月点的测量，观察到应答者组的平均BCVA有所改善，而未应答者的平均BCVA则更差。但是，我们的回归分析 调整混杂因素后，在隐性模型下，nAMD患者的Y402H基因型与治疗反应之间无显着相关性（p> 0.05）。总体而言，我们的结果表明，在马来西亚人群中，除Y402H多态性外，其他因素也可能与抗VEGF药物治疗后的nAMD进程有关。