平面细胞极化通路基因突变与神经管缺陷的关联研究

Association between mutations in planar cell polarity pathway genes and neural tube defects

目的探索平面细胞极化通路(PCP通路)基因突变与神经管缺陷(NTDs)发生风险的关系。方法研究对象来自于2002年起在山西省六个区县募集的NTDs病例及对照。本研究共纳入NTDs病例456例,正常对照459例。在提取病例及对照DNA后,先对NTDs病例的PCP通路基因外显子区进行测序,根据测序结果选取靶向突变位点,然后在对照中进行基因分型。通过χ2检验来检查病例组和对照组之间的基因型分布,采用Logistic回归模型分析基因变异与NTDs之间的关联强度。结果在对照人群中,所有位点的基因型频率均符合Hardy-Weinberg平衡。在调整了母亲年龄、文化程度、职业后,位于SCRIB基因上的rs6558394位点,在显性模式下AG&GG基因型与AA基因型相比,增加了NTDs发生的风险,OR值为1.63(95%CI:1.07,2.47);在共显性模式下,相比AA基因型,AG基因型是NTDs的危险因素,OR值为1.73,95%CI:(1.12,2.68),GG基因型与NTDs发生无关。其余基因的突变未发现与NTDs发生风险相关。结论 SCRIB基因rs6558394位点A->G突变与NTDs发生风险有关,符合显性遗传模式。

Objective To explore the association between mutations in PCP pathway genes and the risk of neural tube defects. Methods The study was based on a population-based birth defect surveillance program in six districts and counties of Shan Xi province since 2002,including 456 cases with neural tube defects（ NTDs） and 459 healthy controls.After extracting DNA of the cases and controls,exonic coding regions of PCP pathway genes in NTDs were sequenced.According to the sequencing results,targeted mutations were selected and genotyped in controls. The χ2 test was used to examine genotype distribution between case and control groups. Logistic regression was performed to analyze the association between gene variation and NTDs. Results Among the control population,genotype frequencies at all loci were in accordance with Hardy-Weinberg equilibrium. After adjusting maternal age,education and occupation levels,the AG GG genotype of rs6558394 located in the SCRIB gene increased the risk of NTDs compared with AA genotype in the dominant model,with an OR of 1. 63（ 1. 07,2. 47）. In the co-dominant model,the genotype of AG was a risk factor for NTDs compared with AA genotype,with an OR of 1. 73（ 1. 12,2. 68）,while GG genotype was not related to risk of NTDs. There were no associations between mutations in other PCP genes and the risk of NTDs. Conclusion The A- G mutation at rs6558394 of the SCRIB gene is associated with the risk of NTDs,consistent with a dominant inheritance pattern.