Association between IRF6 and nonsyndromic cleft lip with or without cleft palate in four populations
Association between IRF6 and nonsyndromic cleft lip with or without cleft palate in four populations
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DOI：
10.1097/gim.0b013e3180423cca
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发表时间：
2007-04-01
影响因子：
8.8
通讯作者：
Beaty, Terri H.
中科院分区：
文献类型：
--
作者：
Park, Ji Wan;McIntosh, Iain;Beaty, Terri H.
目的：干扰素调节因子6（IRF 6），即引起货车德沃德综合征的基因，已被证明与几个人群中的非综合征性唇腭裂（有或无腭）有关。本研究旨在确认IRF 6在其他亚洲人群中对唇裂伴或不伴腭裂风险的贡献。研究方法：一组13个单核苷酸多态性与唇腭裂或无腭77欧洲美国人，146台湾人，34新加坡人，和40韩国的情况下，父母三人使用传递不平衡检验和条件Logistic回归模型进行了测试。结果如下：在所有四个群体中观察到了联系和关联的证据;和两种特异的单倍型[GC由rs 2235373-rs 2235371组成（p.V2741）和rs 599021-rs 2235373-rs 595918的AAG]显示台湾病例中最显著的过度和不足传播（分别为P = 9 x 10（-6）和P = 5 x 10（-6））。在台湾样本中，由rs 599021-rs 2235373-rs 2013162组成的AGC/CGC双倍型的风险增加了近7倍（P < 10（-3））。这些结果证实了该基因在不同人群中对口裂易感性的贡献;然而，显示统计学显著性的特异性单核苷酸多态性在种族群体之间存在差异。结论：这里确定的高风险基因型和双倍型可能会提供一个更好的理解这个基因在口腔裂的病因作用和遗传咨询的潜在选择。
Purpose: The interferon regulatory factor 6 (IRF6), the gene that causes van der Woude syndrome has been shown to be associated with nonsyndromic cleft lip with or without palate in several populations. This study aimed to confirm the contribution of IRF6 to cleft lip with or without palate risk in additional Asian populations. Methods: A set of 13 single nucleotide polymorphisms was tested for association with cleft lip with or without palate in 77 European American, 146 Taiwanese, 34 Singaporean, and 40 Korean case-parent trios using both the transmission disequilibrium test and conditional logistic regression models. Results: Evidence of linkage and association was observed among all four populations; and two specific haplotypes [GC composed of rs2235373-rs2235371 (p.V2741) and AAG of rs599021-rs2235373-rs595918] showed the most significant over- and undertransmission among Taiwanese cases (P = 9 x 10(-6) and P = 5 x 10(-6), respectively). The AGC/CGC diplotype composed of rs599021-rs2235373-rs2013162 showed almost a 7-fold increase in risk among the Taiwanese sample (P < 10(-3)). These results confirmed the contribution of this gene to susceptibility of oral clefts across different populations; however, the specific single nucleotide polymorphisms showing statistical significance differed among ethnic groups. Conclusion: The high-risk genotypes and diplotypes identified here may provide a better understanding of the etiological role of this gene in oral clefts and potential options for genetic counseling.