CTG18.1 Expansion in TCF4 Increases Likelihood of Transplantation in Fuchs Corneal Dystrophy.
CTG18.1 Expansion in TCF4 Increases Likelihood of Transplantation in Fuchs Corneal Dystrophy.
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DOI：
10.1097/ico.0000000000001049
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发表时间：
2017-01
期刊：
影响因子：
2.8
通讯作者：
Gottsch JD
中科院分区：
文献类型：
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作者：
Eghrari AO;Vasanth S;Wang J;Vahedi F;Riazuddin SA;Gottsch JD
富克斯营养不良症是美国角膜移植的主要适应症。TCF4中CTG18.1三核苷酸重复与Fuchs营养不良的严重程度相关；然而，包括年龄和性别影响在内的移植风险增加的定量估计尚不清楚。在一家高等教育机构的临床实践中，574名参与者参加了一项关于Fuchs营养不良的纵向研究，在裂隙灯生物显微镜检查证实双眼存在显著的中央点滴和/或角膜移植后。我们记录了临床病史、检查结果和人口统计学信息。我们采集血样，提取DNA，并对TCF4中CTG18.1三核苷酸重复序列进行测序。在这项回顾性病例对照研究中，评估了有三胞胎扩大的参与者的数量和移植状态。Kaplan-Meier对时间和移植事件的估计被产生。使用COX比例风险回归模型评估年龄、性别、三胞胎扩大和手术之间的关系。共有106名参与者(18.5%)在最初评估时曾接受过至少一只眼的角膜移植。携带等位基因扩展的个体接受移植的比例(78/357，21.8%)高于未携带扩展等位基因的个体(28/217，12.9%)，有显著相关性(p=0.007)。LOG-RANK检验显示生存函数随时间变化有显著差异(P=0.027)，风险比为1.6 4(95%可信区间为1.0 5~2.5 5)。在Fuchs营养不良患者中，TCF4 CTG三核苷酸重复序列的扩大与给定年龄的角膜移植可能性增加1.64倍相关。
Fuchs dystrophy is the leading indication for corneal transplantation in the United States. A CTG18.1 trinucleotide repeat in TCF4 correlates with increased severity in Fuchs dystrophy; however, quantitative estimates of increased transplantation risk, including effects of age and gender, are unclear. In a tertiary institution clinical practice, 574 participants were enrolled in a longitudinal study of Fuchs dystrophy after slit-lamp biomicroscopy confirmed significant central guttae and/or corneal transplantation in both eyes. We documented clinical history, examination findings, and demographic information. We acquired blood samples, extracted DNA and sequenced the CTG18.1 trinucleotide repeat in TCF4. In this retrospective case-control study, the number of participants with triplet expansion, defined as greater than 40 CTG repeats, and transplantation status were assessed. Kaplan-Meier estimates of timing and transplantation events were produced. Cox proportional hazard regression model was utilized to assess for the relationship between age, gender, triplet expansion, and surgery. A total of 106 participants (18.5%) previously underwent corneal transplantation in at least one eye at the time of initial evaluation. A higher proportion of individuals harboring allele expansion had undergone transplantation (78/357, 21.8%) compared to those without the expanded allele (28/217, 12.9%), a significant association (p=0.007). Log-rank test demonstrates a significant difference in survival function over time (p=0.027), with hazard ratio of 1.64 (95% CI, 1.05 to 2.55). Expansion of the TCF4 CTG trinucleotide repeat was associated with 1.64 times higher likelihood of corneal transplantation at a given age in patients with Fuchs dystrophy.