单纯性先天缺牙患者BMP2/BMP4基因位点分析

BMP2/BMP4 genetic evaluation in 40 patients with tooth agenesis

目的:对BMP2/BMP4基因在单纯性先天缺牙患者中的基因表达进行观察,探讨其在先天缺牙疾病中可能的发病机制。方法:提取单纯性先天缺牙患者40例及其家系成员外周静脉血基因组DNA,另选择100例非先天缺牙患者作为对照,应用聚合酶链式反应(PCR)扩增BMP2/BMP4基因编码外显子,纯化、测序,应用DNASTAR软件对测序结果进行对比分析。采用SPSS13.0软件包对数据进行统计学处理。结果:40例先天缺牙患者中,共检测到BMP2/BMP4基因5个突变位点,其中BMP2基因4个突变点:3个错义突变c.109T>G,c.166C>G,c.570A>T,检出率分别为7.5%、2.5%和95%;1个同义突变(c.261A>G),检出率为100%。3个为db SNP数据库中已报道过的多态位点:BMP2SNPs c.109T>G p.Ser37Ala;c.261A>G p.Ser87Ser;c.570A>T p.Arg190Ser;家系先证者BMP2 c.166C>G突变在正常对照组未检出,db SNP数据库未报道,也未被收录于致病基因数据库,为新突变位点。BMP4基因检测出错义突变c.455T>C,检出率为55%,为db SNP数据库中已报道过的多态位点。与对照组等位基因及基因型比较,无显著差异。结论:单纯性先天缺牙可能与BMP2/BMP4基因检出SNPs相关。BMP2c.166C>G杂合突变是新发现的突变,可能是单纯性先天缺牙家系的致病突变。

PURPOSE： To evaluate the potential mutation in BMP2/BMP4 genes in Chinese patients with non-syndromic hypodontia. METHODS： Genomic DNA was isolated from blood samples of 40 non-syndromic hypodontia Chinese patients. One hundred unrelated individuals, who were not affected with tooth agenesis（excluding third molars）, were used as controls. PCR was performed to amplify each exon of BMP2/BMP4 genes. Gel-purified PCR fragments were sequenced to detect mutations. SPSS13.0 software package was used to analyze the data. RESULTS： We identified 4 single nucleotide polymorphisms（SNPs） BMP2, c.109TG p.Ser37Ala; c.261AG p.Ser87Ser; c.570AT p.Arg190Ser;BMP4 c.455 T C p.Val152Ala; and a novel mutation BMP2 c.166 C G p.Arg56 Gly within the family. CONCLUSIONS： Our finding suggests that all the identified SNPs and the new mutation of BMP2 may be responsible for tooth agenesis in the participants, but the possible association requires further research.