Interferon regulatory factor 6 (IRF6) gene variants and the risk of isolated cleft lip or palate
Interferon regulatory factor 6 (IRF6) gene variants and the risk of isolated cleft lip or palate
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DOI：
10.1056/nejmoa032909
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发表时间：
2004-08-19
影响因子：
158.5
通讯作者：
Murray, JC
中科院分区：
文献类型：
--
作者：
Zucchero, TM;Cooper, ME;Murray, JC
背景：唇裂或腭裂（或两者的组合）是一种常见的出生缺陷，由遗传和环境因素混合导致。我们寻找一个特定的遗传因素，有助于这一复杂的性状，通过检查大量的受影响的患者和家庭，并评估一个特定的候选gene.METHODS：我们确定了基因编码干扰素调节因子6（IRF 6）作为候选基因的基础上，它参与了常染色体显性形式的唇腭裂，货车der Woude综合征。该基因中的单核苷酸多态性导致氨基酸位置274（V274 I）处的缬氨酸或异亮氨酸。我们对来自亚洲、欧洲和南美洲10个群体的1968个家系的8003名个体进行了V274 I的传递不平衡检验、单倍型和连锁分析以及病例对照分析，并确定了与IRF 6遗传变异相关的唇腭裂风险。结果：在整个人群数据集中发现了强有力的缬氨酸（V）等位基因过度传递的证据（P < 0.05）。
BACKGROUND:Cleft lip or palate (or the two in combination) is a common birth defect that results from a mixture of genetic and environmental factors. We searched for a specific genetic factor contributing to this complex trait by examining large numbers of affected patients and families and evaluating a specific candidate gene.METHODS:We identified the gene that encodes interferon regulatory factor 6 (IRF6) as a candidate gene on the basis of its involvement in an autosomal dominant form of cleft lip and palate, Van der Woude's syndrome. A single-nucleotide polymorphism in this gene results in either a valine or an isoleucine at amino acid position 274 (V274I). We carried out transmission-disequilibrium testing for V274I in 8003 individual subjects in 1968 families derived from 10 populations with ancestry in Asia, Europe, and South America, haplotype and linkage analyses, and case-control analyses, and determined the risk of cleft lip or palate that is associated with genetic variation in IRF6.RESULTS:Strong evidence of overtransmission of the valine (V) allele was found in the entire population data set (P