EPHA3基因多态性与非综合征性唇腭裂关系研究

发布时间：2018-05-30 01:11

  本文选题：非综合征性唇腭裂 + 病因　； 参考：《首都医科大学》2017年硕士论文

【摘要】：目的本研究的目的是通过SNa PShot技术检测EPHA3基因单核苷酸多态性(Single N ucleotide polymorphism,SNP),探讨EPHA3基因SNPs与非综合征性唇腭裂(non-syndromic cleft of lip with or without palate,NSCL/P)发病的关系。并通过SNPinfo和mi RNASNP在线软件,对潜在的功能性SNPs进行生物信息学分析,初步分析其潜在的功能学意义。方法收集180例NSCL/P患者及167例正常对照个体样本,通过SNa PShot技术检测EPHA3基因5个SNPs(rs7650466、rs1398197、rs17801309、rs1054750和rs7632427),采用Plink软件包分析不同位点的基因型频率是否符合遗传平衡检验;并分析5个位点等位基因及基因型与NSCL/P发病的关系。应用Haplo View软件进行连锁不平衡分析(linkage disequilibrium,LD)及单体型分析。应用SNPinfo和mi RN ASNP在线软件进行生物信息学分析。结果5个单核苷酸多态性位点基因型频率分布均符合遗传平衡检验。LD及单倍型分析发现5个位点之间不存在连锁不平衡现象,不构成单倍型。rs7650466T等位基因频率在NSCL/P(OR=0.245,95%CI=0.159-0.379,Pχ2=2.803×10-11,校正Pχ2=1.401×10-10)及CL/P(OR=0.205,95%CI=0.126-0.333,Pχ2=9.138×10-12,校正Pχ2=4.569×10-11)组间有统计学差异。rs7650466 T等位基因与NSCL/P(OR=0.211,95%CI=0.131-0.338,P=9.763×10-11,校正P=4.881×10-10)和CL/P(OR=0.176,95%CI=0.104-0.297,P=7.234×10-11,校正P=3.617×10-10)发病关联程度较高,rs7650466 T等位基因有保护作用,并且在显性模型逻辑回归中,rs7650466 T等位基因在NSCL/P(校正P=8.18×10-10)和CL/P(校正P=3.139×10-10)中为显性遗传作用。而其余4个SNPs等位基因在各组均无统计学意义,并且这5个SNPs的基因型在各组均无统计学意义。在生物信息学分析中,SNPinfo在线软件分析发现EPHA3基因的rs7650466为mi R-1255a、mi R-125a-3p、mi R-143和mi R-552的潜在匹配位点,并且mi RN ASNP在线软件分析发现,在正常情况下EPHA3-rs7650466 C等位基因与mi R-2052种子区的G等位基因结合,当EPHA3-rs7650466 C突变为T时,EPHA3基因3'-UTR与mi R-2052的结合力可能会降低,导致改变基因的表达水平。结论在中国汉族人群中,EPHA3基因rs7650466与NSCL/P发病相关联,分层分析发现rs7650466与CL/P发病相关联,而与ICP发病无明显相关性。
[Abstract]:The purpose of this study was to detect the relationship between the EPHA3 gene single nucleotide polymorphisms (Single N ucleotide polymorphism, SNP) by SNa PShot technique and the relationship between the EPHA3 gene SNPs and the pathogenesis of non syndromic cleft lip and palate. Functional SNPs was analyzed by bioinformatics, and its potential functional significance was preliminarily analyzed. Methods 180 cases of NSCL/P and 167 normal controls were collected, and 5 SNPs of EPHA3 gene (rs7650466, rs1398197, rs17801309, rs1054750 and rs7632427) were detected by SNa PShot technique, and the genotype frequency of different loci was analyzed by the Plink software package. Whether the rate was consistent with the genetic balance test; and the relationship between 5 alleles and genotypes and the incidence of NSCL/P was analyzed. Haplo View software was used to carry out linkage disequilibrium analysis (linkage disequilibrium, LD) and haplotype analysis. Bioinformatics analysis was carried out with SNPinfo and MI RN ASNP online software. Results of 5 single nucleotide polymorphisms were found. The frequency distribution of point genotypes conformed to genetic balance test.LD and haplotype analysis found that there was no linkage disequilibrium between 5 loci, which did not constitute the frequency of.Rs7650466T alleles of haplotype at NSCL/P (OR=0.245,95%CI=0.159-0.379, P 2=2.803 x, P x 2=1.401 * 10-10) and CL/P (OR=0.205,95%CI=0.126-0.333, P x 2=9.138 * 1). 0-12, the correction of P x 2=4.569 x 10-11) was statistically different between.Rs7650466 T alleles and NSCL/P (OR=0.211,95%CI=0.131-0.338, P=9.763 x 10-11, correction P=4.881 x 10-10) and CL/P (OR=0.176,95%CI=0.104-0.297, P=7.234 x 10-11, correcting P=3.617 x 10-10). In the logistic regression model, rs7650466 T alleles are dominant in NSCL/P (corrected P=8.18 x 10-10) and CL/P (corrected P=3.139 x 10-10). The remaining 4 SNPs alleles are not statistically significant in each group, and the 5 SNPs genotypes have no statistical significance in each group. In bioinformatics analysis, SNPinfo online software It was found that the rs7650466 of the EPHA3 gene was the potential matching site of MI R-1255a, MI R-125a-3p, MI R-143 and MI R-552. In Chinese Han population, EPHA3 gene rs7650466 is associated with the pathogenesis of NSCL/P. Stratified analysis found that rs7650466 is associated with the pathogenesis of CL/P and has no significant correlation with the pathogenesis of ICP.
【学位授予单位】：首都医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R782.2

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本文编号：1953243