Variants in the VEGFA Gene and Treatment Outcome after Anti-VEGF Treatment for Neovascular Age-related Macular Degeneration
Variants in the VEGFA Gene and Treatment Outcome after Anti-VEGF Treatment for Neovascular Age-related Macular Degeneration
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DOI：
10.1016/j.ophtha.2012.10.006
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发表时间：
2013-01-01
期刊：
影响因子：
13.7
通讯作者：
Guymer, Robyn H.
中科院分区：
文献类型：
--
作者：
Abedi, Farshad;Wickremasinghe, Sanjeewa;Guymer, Robyn H.
目的：为了确定VEGFA基因的遗传变异与抗血管内皮生长因子（VEGF）治疗新生血管性年龄相关性黄斑变性（AMD）的结果之间的关系，设计：一项前瞻性队列研究。参与者：我们纳入了201例连续接受抗VEGF注射治疗新生血管性AMD的患者。方法：患者随访超过12个月。他们接受了3次初始每月一次的雷珠单抗或贝伐单抗注射。此后，临床医生在每次随访访视时根据重新治疗标准做出重新治疗的决定。选择并检查VEGFA基因中的7个标记的单核苷酸多态性（tSNPs）。多变量数据分析用于确定每个tSNP在治疗outcome.Main结局Measures中的作用：所选VEGFA tSNP对6个月时视力（VA）结局的影响结果：平均基线VA为51 +/- 17早期治疗糖尿病视网膜病变研究（ETDRS）字母评分。总体而言，第3、6和12个月时VA较基线的平均变化分别为+6.5 +/- 12、+4.4 +/- 13.4和+2.3 +/- 14.6个字母。tSNP rs3025000是唯一显著相关的SNP。治疗3、6和12个月后（与基线相比P= 5个字母）（比值比分别为2.7、3.5和2.4; 95%置信区间分别为1.46-5.07、1.82-6.71和1.27-4.57）。抗VEGF治疗与药物遗传学相关性可能影响新生血管性AMD的视力结局。在tSNP rs3025000中具有T等位基因的患者中，在6个月时有显著更好的视力结果，并且在3、6和12个月时属于抗VEGF治疗的应答组的患者的机会更大。在SNP rs3025000处携带T等位基因的患者的VA结果与关键临床试验的结果相当，但注射较少，使得治疗在某些患者亚组中可能更具成本效益。
Purpose: To determine the association of genetic variants of the VEGFA gene with outcome of anti-vascular endothelial growth factor (VEGF) treatment in neovascular age-related macular degeneration (AMD).Design: A prospective cohort study.Participants: We included 201 consecutive patients receiving anti-VEGF injections for neovascular AMD.Methods: Patients were followed over 12 months. They were treated with 3 initial monthly ranibizumab or bevacizumab injections. Thereafter, the decision to retreat was made by clinicians at each follow-up visit on the basis of retreatment criteria. Seven tagged single nucleotide polymorphisms (tSNPs) in the VEGFA gene were selected and examined. Multivariate data analysis was used to determine the role of each tSNP in treatment outcome.Main Outcome Measures: The influence of selected VEGFA tSNPs on visual acuity (VA) outcome at 6 months.Results: Mean baseline VA was 51 +/- 17 Early Treatment Diabetic Retinopathy Study (ETDRS) letter scores. Overall, the mean change in VA from baseline was +6.5 +/- 12, +4.4 +/- 13.4, and +2.3 +/- 14.6 letters at 3, 6, and 12 months, respectively. The tSNP rs3025000 was the only SNP significantly associated (P= 5 letters from baseline) after 3, 6, and 12 months treatment (odds ratio, 2.7, 3.5, and 2.4; 95% confidence interval, 1.46-5.07, 1.82-6.71, and 1.27-4.57, respectively) than any other outcome group.Conclusions: Pharmacogenetic association with anti-VEGF treatments may influence the visual outcomes in neovascular AMD. In patients with the T allele in tSNP rs3025000, there was a significantly better visual outcome at 6 months and a greater chance of the patients belonging to the responder group with anti-VEGF treatment at 3, 6, and 12 months. The VA outcomes of patients harboring the T allele at SNP rs3025000 were comparable with those of the pivotal clinical trials but with fewer injections, making the treatment perhaps more cost effective in certain subgroups of patients.