Transethnic Replication of Association of CTG18.1 Repeat Expansion of TCF4 Gene With Fuchs' Corneal Dystrophy in Chinese Implies Common Causal Variant
Transethnic Replication of Association of CTG18.1 Repeat Expansion of TCF4 Gene With Fuchs' Corneal Dystrophy in Chinese Implies Common Causal Variant
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DOI：
10.1167/iovs.14-15390
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发表时间：
2014-11-01
影响因子：
4.4
通讯作者：
Mootha, V. Vinod
中科院分区：
文献类型：
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作者：
Xing, Chao;Gong, Xin;Mootha, V. Vinod
目的。为探讨TCF4基因CTG18.1三核苷酸重复序列扩增与Fuchs内皮性角膜营养不良(FECD)的相关性。方法：采用短串联重复序列和三重重复序列启动的聚合酶链式反应方法，对57例FECD患者和121例正常对照进行CTG18.1基因分型。对扩增的CTG18.1等位基因和18个单核苷酸多态(SNPs)与FECD的相关性进行统计学分析。结果扩增的CTG18.1等位基因与FECD相关(P=4.7x10(-14))，每个拷贝的优势比估计为66.5(95%可信区间：12.6~350.1)。有5个TCF4 SNP在名义水平上与FECD相关(P<；5.0×10(-2))；然而，根据扩展的CTG18.1多态，没有一个SNP与FECD相关。结论TCF4基因中CTG18.1重复扩增与FECD之间的关联的跨结构复制表明，它是一种在欧亚人群中共有的常见的因果变异，具有发生FECD的显著风险。我们的数据表明，在中国人群中，扩展的CTG18.1等位基因是该基因座的主要(如果不是唯一的)因果变异。
PURPOSE. To test the association between the CTG18.1 trinucleotide repeat expansion of TCF4 gene and Fuchs' endothelial corneal dystrophy (FECD) in a Chinese population.METHODS. The trinucleotide repeat polymorphism CTG18.1 was genotyped using short tandem repeat and triplet repeat primed polymerase chain reaction assays in 57 Chinese subjects with FECD and 121 controls. Statistical association of the expanded CTG18.1 allele and 18 single nucleotide polymorphisms (SNPs) across TCF4 with FECD was evaluated. To investigate the linkage disequilibrium structure of the TCF4 region, haplotype analysis was performed on our study subjects and compared with genotyping data of 97 Han Chinese and 85 Caucasians in the 1000 Genomes Project.RESULTS. The expanded CTG18.1 allele was associated with FECD (P = 4.7 x 10(-14)), with the odds ratio of each copy of the expanded allele estimated to be 66.5 (95% confidence interval: 12.6-350.1). Five TCF4 SNPs showed association with FECD at a nominal level (P < 5.0 x 10(-2)); however, conditional on the expanded CTG18.1 polymorphism, none of the SNPs showed association with FECD. The only haplotype associated with the disease was the one with the expansion at the CTG18.1 locus.CONCLUSIONS. Transethnic replication of the association between the CTG18.1 repeat expansion in the TCF4 gene and FECD suggests it is a common, causal variant shared in Eurasian populations conferring significant risk for the development of FECD. Our data suggest that the expanded CTG18.1 allele is the main, if not sole, causal variant at this gene locus in the Chinese population.