Genetic variants in IRF6 and the risk of facial clefts: single-marker and haplotype-based analyses in a population-based case-control study of facial clefts in Norway.
Genetic variants in IRF6 and the risk of facial clefts: single-marker and haplotype-based analyses in a population-based case-control study of facial clefts in Norway.
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DOI：
10.1002/gepi.20314
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发表时间：
2008-07
影响因子：
2.1
通讯作者：
Murray, Jeffrey C.
中科院分区：
文献类型：
--
作者：
Jugessur, Astanand;Rahimov, Fedik;Lie, Rolv T.;Wilcox, Allen J.;Gjessing, Hakon K.;Nilsen, Roy M.;Nguyen, Truc Trung;Murray, Jeffrey C.
关键词：
编码干扰素调节因子6 （IRF6）的基因突变是一种常见的综合征裂型，即Van der Woude综合征的基础。唇坑和缺牙是唯一的额外特征区分综合征从孤立的唇裂。因此，Van der Woude综合征为研究分离形式的裂裂提供了一个极好的模型。从1996-2001年挪威以人群为基础的面部腭裂病例对照研究中，我们选择了377例伴有或不伴有腭裂的唇裂（CL/P）， 196例单纯腭裂（CPO）和763例对照婴儿-父母三联体进行分析。我们对IRF6基因座内的6个单核苷酸多态性进行了基因分型，并估计了孩子和母亲的等位基因和单倍型赋予孩子的相对风险（RR）。总的来说，在我们的数据中，与CL/P有很强的统计学相关性，而与CPO没有统计学相关性。在单标记分析中，在rs4844880位点有双剂量“a”等位基因的母亲生下CL/P的风险增加（RR = 1.85, 95%可信区间：1.04-3.25;P = 0.036）。当儿童携带单剂量的rs2235371等位基因（p.V274I多态性）时，获得的RR为0.38（95%置信区间：0.16-0.92;P = 0.031）。总体检验的p值<0.001。在单倍型分析中，胎儿和母亲的一些单倍型相对风险在个体上有统计学意义，但不足以显示在整体测试中（P = 0.113）。综上所述，这些发现进一步支持了IRF6变异在唇裂中的作用，并提供了挪威人群中具体的风险估计。
Mutations in the gene encoding interferon regulatory factor 6 (IRF6) underlie a common form of syndromic clefting known as Van der Woude syndrome. Lip pits and missing teeth are the only additional features distinguishing the syndrome from isolated clefts. Van der Woude syndrome, therefore, provides an excellent model for studying the isolated forms of clefting. From a population-based case-control study of facial clefts in Norway (1996–2001), we selected 377 cleft lip with or without cleft palate (CL/P), 196 cleft palate only (CPO), and 763 control infant-parent triads for analysis. We genotyped six single nucleotide polymorphisms within the IRF6 locus and estimated the relative risks (RR) conferred on the child by alleles and haplotypes of the child and of the mother. On the whole, there were strong statistical associations with CL/P but not CPO in our data. In single-marker analyses, mothers with a double-dose of the ‘a’-allele at rs4844880 had an increased risk of having a child with CL/P (RR = 1.85, 95% confidence interval: 1.04–3.25; P = 0.036). An RR of 0.38 (95% confidence interval: 0.16–0.92; P = 0.031) was obtained when the child carried a single-dose of the ‘a’-allele at rs2235371 (the p.V274I polymorphism). The P-value for the overall test was <0.001. In haplotype analyses, several of the fetal and maternal haplotype relative risks were statistically significant individually but were not strong enough to show up on the overall test (P = 0.113). Taken together, these findings further support a role for IRF6 variants in clefting of the lip and provide specific risk estimates in a Norwegian population.
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