女性苗勒氏管发育异常与相关基因单核苷酸多态性位点的关联性研究

发布时间：2018-10-26 21:28

【摘要】：目的:苗勒氏管发育异常(Müllerian duct anomalies,MDAs)是指在胚胎发育时期由于苗勒氏管发育停滞、不良或融合、吸收不全而引起的一类先天性女性生殖系统畸形的疾病。本实验主要探索女性苗勒氏管发育异常的发病与相关候选基因单核苷酸多态性位点的遗传学联系。方法:本实验收集我院经宫腹腔镜或输卵管造影确诊的苗勒氏管发育异常的患者的外周血标本362例,收集406例因输卵管因素或是男方因素不孕的苗勒氏管发育正常的女性的外周血标本作为对照,提取所有外周血白细胞中的DNA备用。利用1000 genome数据库和Hap Map数据库挑选针对HOXA9(rs7810502),HOXA13(rs757181),WNT5A(rs7622120),WNT9B(rs12601196,rs4968280),KISS1(rs2510,rs4889),RARA(rs482284,rs9303286),LHX1(rs3785949),EMX2(rs2240776),CFTR(rs213950),RARG(rs6580936,rs941138,rs1465058)这10个基因的15个单核苷酸多态性(single nucleotide polymorphism,SNP)位点,使用Sequenome Massarray质谱阵列技术对这些位点进行分型并采集数据,并在病例组及对照组之间应用SPSS13.0统计软件进行位点基因型分布及等位基因频率的统计学比较。结果:根据纳入标准剔除4个SNP位点(rs7810502,rs757181,rs7622120,rs4889)后,对剩余的11个SNP位点在两组间进行基因型频率及等位基因频率的分析,发现WNT9B基因的rs4968280位点的基因型分布在两组之间存在统计学差异(P0.05),在显性模型中,TC+CC基因型增加了患病的风险。但经过Bonferroni检验校正后,该位点则不具有统计学差异。其余位点的基因型分布及等位基因频率在两组之间并无统计学差异。结论:WNT9B基因的rs4968280位点的变异是否影响女性苗勒氏管发育异常的遗传易感性,仍需要进一步的研究;其余SNP位点的变异可能与苗勒氏管发育异常的发病无关。
[Abstract]:Objective: M 眉 llerian duct anomalies,MDAs is a kind of congenital malformation of the female reproductive system, which is caused by the malformation, malfunction and absorption of the Mellerian duct during embryonic development. This study was designed to explore the genetic association between the pathogenesis of female Muller's tube dysplasia and the single nucleotide polymorphism (SNP) loci of candidate genes. Methods: 362 peripheral blood samples of patients with abnormal development of Muller's canal diagnosed by hysteroscopy or salpingography in our hospital were collected. The peripheral blood samples of 406 infertile women with normal development of Mullerian canal due to fallopian tube or male factors were collected as control. DNA from all peripheral white blood cells were extracted. Using the 1000 genome database and the Hap Map database to select for HOXA9 (rs7810502), HOXA13 (rs757181), WNT5A (rs7622120), WNT9B (rs12601196,rs4968280), KISS1 (rs2510,rs4889), RARA (rs482284,rs9303286), LHX1 (rs3785949), EMX2 (rs2240776), CFTR (rs213950), RARG (rs6580936,rs941138,) Rs1465058), 15 single nucleotide polymorphic (single nucleotide polymorphism,SNP (SNP) loci of the 10 genes were genotyped by Sequenome Massarray mass spectrometry array and data were collected. The genotype distribution and allele frequency were analyzed by SPSS13.0 software. Results: after 4 SNP loci (rs7810502,rs757181,rs7622120,rs4889) were excluded according to the inclusion criteria, the genotypic and allelic frequencies of the remaining 11 SNP loci were analyzed between the two groups. It was found that the genotype distribution of rs4968280 locus of WNT9B gene was significantly different between the two groups (P0.05), and the genotype of, TC CC increased the risk of disease in dominant model. However, there was no statistical difference in this locus after Bonferroni test. There was no significant difference in genotype distribution and allele frequency between the two groups. Conclusion: it is necessary to further study whether the variation of rs4968280 locus of WNT9B gene affects the genetic susceptibility of female Mullerian tube dysplasia, and the variation of other SNP loci may not be related to the pathogenesis of Maller's tube dysplasia.
【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R711.1

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