PDF(Pubmed)
Abstract：
UNASSIGNED: This analysis investigated potential associations between gene variants and clinical end points in the VIEW 1 and 2 randomized clinical trials of intravitreal aflibercept and ranibizumab in neovascular age-related macular degeneration (AMD).
UNASSIGNED: A genome-wide association analysis was conducted in a subgroup of patients from VIEW 1 and 2 consenting to the optional pharmacogenetic analysis.
UNASSIGNED: Data were pooled from 780 samples from patients representative of the overall VIEW 1 and 2 populations. After Bonferroni correction for multiplicity and statistical adjustment for baseline risk factors, no significant associations were found between previously identified prognostic AMD gene variants and treatment response according to key prespecified VIEW 1 and 2 end points. Genome-wide, there were no significant genetic associations in patients experiencing gains of ≥15 Early Treatment of Diabetic Retinopathy Study letters after 1 or 2 years of treatment. A cluster of variants in ANO2 (encoding anoctamin 2, a calcium-activated chloride channel expressed on photoreceptor cells) on chromosome 12 reached the level of significance for loss of ≥5 letters after 1 year of treatment (P < 5 × 10-8), with the ANO2 rs2110166 SNP demonstrating highly significant association (P = 1.99 × 10-8). Carriers of the ANO2 rs2110166 TT genotype showed a robust increase in visual acuity versus baseline compared with a small decrease in those with the TC genotype.
UNASSIGNED: None of the potential prognostic candidate genes were associated with the clinical end points for treated patients. Preliminary analyses suggest an association of ANO2 with retinal function, with a potential impact on vision of approximately one line over at least the first year. Further investigation of the function of ANO2 in retinal pathophysiology is merited.
UNASSIGNED: A genome-wide association analysis was conducted in a subgroup of patients from VIEW 1 and 2 consenting to the optional pharmacogenetic analysis.
UNASSIGNED: Data were pooled from 780 samples from patients representative of the overall VIEW 1 and 2 populations. After Bonferroni correction for multiplicity and statistical adjustment for baseline risk factors, no significant associations were found between previously identified prognostic AMD gene variants and treatment response according to key prespecified VIEW 1 and 2 end points. Genome-wide, there were no significant genetic associations in patients experiencing gains of ≥15 Early Treatment of Diabetic Retinopathy Study letters after 1 or 2 years of treatment. A cluster of variants in ANO2 (encoding anoctamin 2, a calcium-activated chloride channel expressed on photoreceptor cells) on chromosome 12 reached the level of significance for loss of ≥5 letters after 1 year of treatment (P < 5 × 10-8), with the ANO2 rs2110166 SNP demonstrating highly significant association (P = 1.99 × 10-8). Carriers of the ANO2 rs2110166 TT genotype showed a robust increase in visual acuity versus baseline compared with a small decrease in those with the TC genotype.
UNASSIGNED: None of the potential prognostic candidate genes were associated with the clinical end points for treated patients. Preliminary analyses suggest an association of ANO2 with retinal function, with a potential impact on vision of approximately one line over at least the first year. Further investigation of the function of ANO2 in retinal pathophysiology is merited.
摘要：
■该分析调查了玻璃体内阿柏西普和雷珠单抗治疗新生血管性年龄相关性黄斑变性（AMD）的VIEW1和2随机临床试验中基因变异与临床终点之间的潜在关联。
■在符合可选的药物遗传学分析的VIEW1和2患者亚组中进行了全基因组关联分析。
■数据来自来自代表总体视图1和2群体的患者的780个样本。在Bonferroni对多重性进行校正并对基线风险因素进行统计调整后，根据关键预设的VIEW1和2终点,在先前确定的预后性AMD基因变异与治疗反应之间未发现显著关联.全基因组,在治疗1年或2年后,出现≥15篇糖尿病视网膜病变早期治疗研究报告的患者没有显著的遗传关联.在12号染色体上的一组ANO2变体（编码在感光细胞上表达的钙激活的氯化物通道2）在治疗1年后达到≥5个字母丢失的显著性水平（P<5×10-8），与ANO2rs2110166SNP表现出极显著关联(P=1.99×10-8)。与TC基因型的携带者相比，ANO2rs2110166TT基因型的携带者的视敏度相对于基线显示出强劲的增加，而TC基因型的携带者则略有减少。
■没有一个潜在的预后候选基因与治疗患者的临床终点相关。初步分析表明ANO2与视网膜功能有关，至少在第一年对视力有大约一条线的潜在影响。值得进一步研究ANO2在视网膜病理生理学中的功能。
■在符合可选的药物遗传学分析的VIEW1和2患者亚组中进行了全基因组关联分析。
■数据来自来自代表总体视图1和2群体的患者的780个样本。在Bonferroni对多重性进行校正并对基线风险因素进行统计调整后，根据关键预设的VIEW1和2终点,在先前确定的预后性AMD基因变异与治疗反应之间未发现显著关联.全基因组,在治疗1年或2年后,出现≥15篇糖尿病视网膜病变早期治疗研究报告的患者没有显著的遗传关联.在12号染色体上的一组ANO2变体（编码在感光细胞上表达的钙激活的氯化物通道2）在治疗1年后达到≥5个字母丢失的显著性水平（P<5×10-8），与ANO2rs2110166SNP表现出极显著关联(P=1.99×10-8)。与TC基因型的携带者相比，ANO2rs2110166TT基因型的携带者的视敏度相对于基线显示出强劲的增加，而TC基因型的携带者则略有减少。
■没有一个潜在的预后候选基因与治疗患者的临床终点相关。初步分析表明ANO2与视网膜功能有关，至少在第一年对视力有大约一条线的潜在影响。值得进一步研究ANO2在视网膜病理生理学中的功能。
