Association between high-risk disease loci and response to anti-vascular endothelial growth factor treatment for wet age-related macular degeneration.
Association between high-risk disease loci and response to anti-vascular endothelial growth factor treatment for wet age-related macular degeneration.
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DOI：
10.1097/iae.0b013e31822a2c7c
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发表时间：
2012-01
期刊：
影响因子：
--
通讯作者：
Stambolian D
中科院分区：
文献类型：
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作者：
Orlin A;Hadley D;Chang W;Ho AC;Brown G;Kaiser RS;Regillo CD;Godshalk AN;Lier A;Kaderli B;Stambolian D
研究CFH、ARMS2和HTRA1基因中已知的年龄相关性黄斑变性遗传风险变异与抗血管内皮生长因子(VEGF)(雷尼比珠单抗或贝伐单抗)治疗湿性年龄相关性黄斑变性的疗效之间是否存在关联。对150例湿性老年性黄斑变性患者的临床检查和荧光素血管造影资料进行了回顾分析。患者接受雷尼贝珠单抗和/或贝伐单抗的抗血管内皮生长因子治疗。对患者进行了单核苷酸多态rs1061170、rs10490924、rs3750848、rs3793917、rs11200638和rs932275以及跨越CFH、ARMS2和HTRA1基因的内部del443ins54的基因分型。抗血管内皮生长因子治疗阴性者57例，阳性反应者93例。两组之间的平均基线视力没有显著差异。对阴性应答者进行了平均24.0个月的跟踪，对阳性应答者进行了平均22.0个月的跟踪。尽管阳性应答者的高危等位基因频率高于阴性应答者，但这并未达到统计学意义。此外，在两组应答者中，基因分型与注射次数或视力的绝对变化之间没有显著的相关性。在我们的患者队列中，在阳性应答组和阴性应答组中，抗血管内皮生长因子治疗的反应与基因型之间没有统计学意义的相关性。有必要进行更大规模的研究，以进一步确定湿性老年性黄斑变性与抗血管内皮生长因子治疗之间是否存在药物遗传学联系。
To investigate whether there is an association between known age-related macular degeneration genetic risk variants in the CFH, ARMS2, and HTRA1 genes and response to anti-vascular endothelial growth factor (VEGF) (ranibizumab or bevacizumab) treatment for wet age-related macular degeneration. A retrospective review of 150 patients with documented wet age-related macular degeneration based on clinical examination and fluorescein angiogram was performed. Patients received anti-VEGF therapy with ranibizumab and/or bevacizumab. Patients were genotyped for the single-nucleotide polymorphism rs1061170, rs10490924, rs3750848, rs3793917, rs11200638, and rs932275 and for the indel del443ins54 spanning the CFH, ARMS2, and HTRA1 genes. There were 57 patients who were characterized as negative responders to anti-VEGF therapy, and 93 patients who were characterized as positive responders. There was no significant difference in mean baseline visual acuity between the groups. Negative responders were followed for a mean duration of 24.0 months, while positive responders were followed for a mean duration of 22.0 months. Although the frequency of the at-risk alleles was higher in the positive responders when compared with the negative responder, this did not reach statistical significance. Additionally, there was no significant association between genotype and the number of injections or absolute change in visual acuity in both groups of responders. In our patient cohort, there was no statistically significant association between response to anti-VEGF therapy and the genotype in both positive-responder and negative-responder groups. Larger studies with more power are necessary to further determine whether a pharmacogenetic association exists between wet age-related macular degeneration and anti-VEGF therapy.