WNT5B基因与人类神经管畸形(NTDs)的相关性  

The association between WNT5B gene and human neural tube defects(NTDs)

作　　者：周翔宇[1] 杨雪艳[1] 聂晨霞[2] 陈瑛[3] 王红艳[1] 李红[3] 

机构地区：[1]复旦大学生命科学学院遗传工程国家重点实验室-现代人类学教育部重点实验室,上海200433 [2]长治医学院生物教研室,苏州215002 [3]苏州市立医院生殖与遗传中心,长治046000

出　　处：《复旦学报（医学版）》2012年第1期18-24,共7页Fudan University Journal of Medical Sciences

基　　金：上海市自然科学基金面上项目(09ZR1404400);教育部博士点新教师基金(20090071120037)~~

摘　　要：目的探讨WNT5B基因序列变异与人类神经管畸形(neural tube defects,NTDs)发生的相关性。方法应用PCR-Sequencing和SNaPshot技术在163例NTDs患者和357例对照人群中进行WNT5B基因突变扫描和关联分析。结果在NTDs患者的WNT5B基因中共检测到3个新发现的序列变异位点:c.-57-123G>A、c.622-38G>A和c.622-99C>T。其中,c.-57-123G>A位点变异在357例对照人群中未检测到,其为NTDs患者所特有的变异位点。对rs2270036(c.329-16T>C)、rs6489313(c.329-84G>A)和rs58317077(c.329-122T>C)这3个SNP位点的关联分析结果表明:在显性遗传模式下,rs58317077位点的C等位基因与NTDs的发生显著相关,携带C/C或C/T基因型的个体的患病风险是携带T/T基因型的个体的1.62倍(OR=1.62,95%CI=1.05～2.52,P=0.028);生物信息学预测结果表明:rs58317077位点的C等位基因会改变转录因子NF-kap和MZF1对该区域的结合。结论 c.-57-123G>A和rs58317077位点的C等位基因是人类NTDs发生的遗传性风险因子。Objective To explore the association between variants in WNT5B gene and human neural tube defects（NTDs）. Methods Mutation scanning and case-control study were carried out in 163 NTDs patients and 357 control participants through PCR-sequencing and SNaPshot. Results Three new variants,c.-57-123GA,c.622-38GA and c.622-99CT,were identified in WNT5B gene of NTDs patients.Among them,c.-57-123GA was a disease-specific variant which was not detected in all control participants.Association study on rs2270036,rs6489313 and rs58317077 demonstrated that C allele in rs58317077 was significantly associated with NTDs in dominant mode.Individuals with C/C and C/T genotype had 1.62-fold risk to be affected by NTDs than those bearing T/T alleles（OR=1.62,95%CI：1.05-2.52,P=0.028）.Bioinformatics analysis indicated that C allele in rs58317077 would attenuate the binding affinity of transcription factors NF-kap and MZF1 compared with T allele. Conclusions C alleles in c.-57-123GA and rs58317077 are genetic risk factors in human NTDs.

关 键 词：神经管畸形(NTDs) 平面细胞极性信号通路 WNT5B基因 变异位点 突变 

分 类 号：R394.3[医药卫生—医学遗传学]