波兰人群中已报道的候选基因或区域的遗传变异与唇裂伴或不伴腭裂风险之间的关联。

Association between genetic variants of reported candidate genes or regions and risk of cleft lip with or without cleft palate in the polish population.

作者信息

Mostowska Adrianna, Hozyasz Kamil K, Wojcicki Piotr, Biedziak Barbara, Paradowska Patrycja, Jagodzinski Pawel P

机构信息

Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, Poland.

出版信息

Birth Defects Res A Clin Mol Teratol. 2010 Jul;88(7):538-45. doi: 10.1002/bdra.20687.

DOI:10.1002/bdra.20687

PMID:20544801

Abstract

BACKGROUND

Cleft lip with or without cleft palate (CL/P) is one of the most common craniofacial malformations, with a complex and multifactorial etiology. Because of the genetic heterogeneity of facial clefts, the aim of this study was to investigate the contribution of previously reported candidate genes and chromosomal loci to the risk of CL/P in the Polish population.

METHODS

We performed an analysis of 18 polymorphisms of FOXE1, IRF6, MSX1, PAX9, TBX10, FGF10, FGFR1, TGFalpha, TGFbeta3, SUMO1, and the chromosomal region 8q24 in a group of 175 patients with CL/P and a properly matched control group.

RESULTS

Highly significant results were observed for the IRF6 rs642961 variant and the 8q24 region's rs987525 (odds ratio OR, 1.635; 95% confidence interval [CI], 1.153-2.319; p = 0.005; and OR(AC+AAvsCC), 1.962; 95% CI, 1.382-2.785; p = 1.4 x 10(-4), respectively). For rs987525, the results were also significant after correction for multiple comparisons. Borderline association with an increased risk of CL/P was also identified for the SUMO1 locus (rs2350350; OR(CGvsGG), 1.580; 95% CI, 1.056-2.363; p = 0.025).

CONCLUSIONS

Our findings confirmed that genetic variants of IRF6 and the polymorphism located in the 8q24 gene desert are strongly involved in the etiology of facial clefts in the Polish population sample.

摘要

背景

唇裂伴或不伴腭裂（CL/P）是最常见的颅面畸形之一，其病因复杂且具有多因素性。由于面部裂隙存在遗传异质性，本研究旨在调查先前报道的候选基因和染色体位点对波兰人群中CL/P风险的影响。

方法

我们对175例CL/P患者及匹配良好的对照组进行了分析，检测了FOXE1、IRF6、MSX1、PAX9、TBX10、FGF10、FGFR1、TGFalpha、TGFbeta3、SUMO1的18个多态性位点以及染色体区域8q24。

结果

观察到IRF6基因的rs642961变异和8q24区域的rs987525具有高度显著结果（优势比[OR](AG + AA对GG)，1.635；95%置信区间[CI]，1.153 - 2.319；p = 0.005；以及OR(AC + AA对CC)，1.962；95% CI，1.382 - 2.785；p = 1.4×10⁻⁴）。对于rs987525，经多重比较校正后结果仍显著。还发现SUMO1基因座（rs2350350）与CL/P风险增加存在临界关联（OR(CG对GG)，1.580；95% CI，1.056 - 2.363；p = 0.025）。