Department of Ophthalmology, University of Ferrara, Ferrara, Italy.
Ophthalmology. 2010 Mar;117(3):517-23. doi: 10.1016/j.ophtha.2009.08.028. Epub 2009 Dec 30.
To investigate whether different coagulation-balance genetic backgrounds might explain the variable clinical outcomes detected, after a single photodynamic therapy with verteporfin (PDT-V), in Caucasian patients with subfoveal choroidal neovascularization (CNV) secondary to pathologic myopia (PM).
Retrospective, consecutive, nonrandomized, interventional cases series.
Two hundred thirty-four patients exclusively treated with standardized PDT-V for the presence of PM-related classic CNV.
The enrolled patients were subdivided as responders or nonresponders based on CNV responsiveness to the first PDT-V over a 3-month period. Three common gene polymorphisms, factor XIII-A G185T, methylenetetrahydrofolate reductase C677T, and methionine synthase reductase A66G, were genotyped by polymerase chain reaction in each patient.
The measures of CNV responsiveness to PDT-V were the changes, respect to baseline, of fluorescein angiography CNV leakage, greatest linear dimension, and area of the lesion. Logistic regression analyses were performed to explore the predictive role of phenotypic (patient's age, baseline visual acuity, and baseline CNV area) and genotypic (all the mentioned mutations) variables regarding PDT-V efficacy.
Responders to PDT-V were overrepresented within carriers of methylenetetrahydrofolate reductase 677 T-allele (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.8-5.4; P = 0.001) and, to a minor extent, among patients with better visual acuity at baseline (OR, 11.8; 95% CI, 1.6-88.0; P = 0.02). However, predictors of PDT-V lack of efficacy were patient's age (OR, 0.73; 95% CI, 0.62-0.86; P = 0.01) and, especially, factor XIII-A 185 GT/TT genotypes (OR, 0.19; 95% CI, 0.11-0.35; P = 0.0001). All the other considered predictive factors did not significantly influence the CNV responsiveness to PDT-V.
These findings document the presence of pharmacogenetic correlations between common coagulation-balance gene polymorphisms and different CNV responsiveness to PDT-V in Caucasian patients with neovascular PM.
研究不同的凝血平衡遗传背景是否可以解释在接受单一光动力疗法（PDT-V）治疗后，患有与病理性近视（PM）相关的脉络膜新生血管（CNV）的白人患者中，检测到的可变临床结果。
回顾性、连续、非随机、干预性病例系列研究。
234 名患者仅接受标准化 PDT-V 治疗，以治疗 PM 相关经典 CNV。
根据 3 个月内 PDT-V 对 CNV 的反应，将纳入的患者分为应答者或无应答者。通过聚合酶链反应在每位患者中对三种常见基因多态性，即因子 XIII-A G185T、亚甲基四氢叶酸还原酶 C677T 和蛋氨酸合成酶还原酶 A66G 进行基因分型。
评估 PDT-V 对 CNV 反应的措施为荧光素血管造影 CNV 渗漏、最大线性尺寸和病变面积与基线相比的变化。进行逻辑回归分析，以探索表型（患者年龄、基线视力和基线 CNV 面积）和基因型（所有提到的突变）变量对 PDT-V 疗效的预测作用。
对 PDT-V 有反应的患者在携带亚甲基四氢叶酸还原酶 677 T-等位基因的患者中占优势（优势比[OR]，3.1；95%置信区间[CI]，1.8-5.4；P = 0.001），并且在基线视力较好的患者中也占优势（OR，11.8；95%CI，1.6-88.0；P = 0.02）。然而，PDT-V 无效的预测因子是患者的年龄（OR，0.73；95%CI，0.62-0.86；P = 0.01），特别是因子 XIII-A 185 GT/TT 基因型（OR，0.19；95%CI，0.11-0.35；P = 0.0001）。所有其他考虑的预测因素均未显著影响 PDT-V 对 CNV 的反应。
这些发现证明了在患有新生 PM 的白人患者中，常见凝血平衡基因多态性与不同的 PDT-V 对 CNV 反应之间存在药物遗传学相关性。
