Genetic Risk Factors for Nonsyndromic Cleft Lip with or without Cleft Palate in a Mesoamerican Population: Evidence for IRF6 and Variants at 8q24 and 10q25
Genetic Risk Factors for Nonsyndromic Cleft Lip with or without Cleft Palate in a Mesoamerican Population: Evidence for IRF6 and Variants at 8q24 and 10q25
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DOI：
10.1002/bdra.20689
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发表时间：
2010-07-01
影响因子：
--
通讯作者：
Mangold, Elisabeth
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文献类型：
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作者：
Rojas-Martinez, Augusto;Reutter, Heiko;Mangold, Elisabeth
前言：非综合征性唇裂伴或不伴腭裂(NSCL/P)是最常见的出生缺陷之一。NSCL/P的病因是多因素的，既包括遗传因素也包括环境因素。IRF6基因和位于8q24、10q25和17q22的另外三个易感基因是欧洲血统患者NSCL/P的遗传危险因素。方法：采用病例对照关联研究方法，以4个单核苷酸多态代表IRF6和3个新的易感基因座，研究这4个危险基因座是否与中美洲人群的NSCL/P有关。共有149名NSCL/P患者和303名玛雅人对照纳入研究。结果：单标记分析显示，NSCL/P与IRF6、8q24和10q25基因座的风险变异显著相关。与以前的发现相反，8q24基因座的关联完全由风险等位基因的纯合子携带者驱动。这表明该基因座可能在玛雅人中以隐性的方式起作用。在17q22基因座上没有发现关联的证据。这可能是由于样本的力量有限所致。结论：IRF6、10q25和8q24基因座与玛雅血统人群NSCL/P的发生有关。出生缺陷研究(A部分)88：-537,2010。(C)2010年Wiley-Liss公司
INTRODUCTION: Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is one of the most common of all birth defects. NSCL/P has a multifactorial etiology that includes both genetic and environmental factors. The IRF6 gene and three further susceptibility loci at 8q24, 10q25, and 17q22, which were identified by a recent genome-wide association scan (GWAS), are confirmed genetic risk factors for NSCL/P in patients of European descent. METHODS: A case-control association study was performed to investigate whether these four risk loci contribute to NSCL/P in a Mesoamerican population using four single nucleotide polymorphisms to represent IRF6 and the three novel susceptibility loci. A total of 149 NSCL/P patients and 303 controls of Mayan origin were included. RESULTS: Single marker analysis revealed a significant association between NSCL/P and risk variants in IRF6 and the 8q24 and 10q25 loci. In contrast to previous findings, the association at the 8q24 locus was driven solely by homozygote carriers of the risk allele. This suggests that this locus might act in a recessive manner in the Mayan population. No evidence for association was found at the 17q22 locus. This may have been attributable to the limited power of the sample. CONCLUSION: These results suggest that IRF6 and the 10q25 and 8q24 loci confer a risk for the development of NSCL/P in persons of Mayan origin. Birth Defects Research (Part A) 88:535-537, 2010. (C) 2010 Wiley-Liss, Inc.