VEGF基因多态性与复发性自然流产（RSA）的关联性研究

发布时间：2018-03-04 01:00

本文选题：血管内皮生长因子（VEGF）　切入点：基因多态性　出处：《宁夏医科大学》2014年硕士论文　论文类型：学位论文

【摘要】：目的本研究旨在探讨血管内皮生长因子（vascular endothelial growth factor,VEGF）基因rs699947(C/A),rs1570360(G/A)，rs833061(T/C)和rs3025039(C/T)四个多态性位点与中国宁夏地区汉族妇女复发性自然流产（recurrent spontaneous abortion, RSA）的相关性，并分析VEGF基因的四个SNP位点所构建的单倍型与复发性自然流产之间的关联性。方法病例组选取2006年1月至2009年7月在宁夏医科大学生殖与遗传实验室进行染色体检查的复发性自然流产患者203例，年龄19-42岁，平均年龄27.63±4.44岁；对照组选取与病例组年龄相匹配的2008年1月至2010年10月在银川市妇幼保健院正常分娩的女性190例，年龄20-36岁，平均年龄27.26±2.31岁。采用聚合酶链反应-限制性片段长度多态性（polymerase chain-reaction restricted fragment length polymorphism,PCR-RFLP）和等位基因特异性PCR（AS-PCR）技术检测病例组与对照组VEGF基因四个位点多态性。用SPSS18.0统计软件进行卡方检验及疾病相对危险度的估计，计算和比较各组基因型频率、等位基因频率、比值比（OR）及95%可信区间（95%CI），分析VEGF基因四个SNPs位点与复发性自然流产的相关性，用Haploview软件进行连锁不平衡及单倍体型分析，探讨VEGF基因四个SNPs位点与复发性自然流产易感性之间的关联。结果①经遗传平衡定律检验，VEGF基因的四个多态性位点中除rs1570360外，其余位点各基因型频率分布均符合Hardy-Weinberg平衡法则，具有群体代表性。②VEGF基因rs833061的基因型与等位基因分布频率在病例组和对照组中进行比较，结果显示差异均有统计学意义（P0.001）。VEGF基因rs3025039的基因型与等位基因分布频率在病例组和对照组中进行比较，结果显示差异均有统计学意义（P0.01）。③VEGF基因rs699947、rs1570360位点各基因型频率和等位基因频率在病例组与对照组中的分布均无统计学意义（P0.05）。④VEGF基因rs699947、rs833061与rs3025039三个位点构建的单倍型中有5种保护性单倍型在病例组与对照组中具有统计学意义（P0.05，OR1）；5种危险致病单倍型在两组中的分布具有统计学差异（P0.05，OR1）。结论1、VEGF基因rs699947、rs1570360位点的基因多态性与宁夏汉族女性复发性自然流产的易感性无关。2、VEGF基因rs833061、rs3025039位点的基因多态性与复发性自然流产有一定的关联性，携带rs833061T及rs3025039T等位基因的基因型可能是宁夏汉族女性复发性自然流产的易感因素。3、VEGF基因构建的单倍型中，有5种单倍型可能是宁夏汉族女性复发性自然流产的保护性因素，有5种单倍型可能是宁夏汉族女性复发性自然流产的危险性因素。目的对VEGF基因多态性与复发性自然流产相关性研究的现有数据进行评估和综合。方法通过文献检索收集国内外数据库自开库至2013年11月公开发表的关于VEGF基因多态性与复发性自然流产相关性的病例-对照研究，剔除不符合要求的文献，采用RevMan5.2软件，根据文献异质性检验结果，进行固定效应模型和随机效应模型的Meta分析。对不同纳入标准的结果进行了敏感性分析，用漏斗图评估发表性偏倚。结果纳入符合标准的已发表文献11篇、未发表文献1篇（本研究），，其中涉及rs1570360(G/A)多态性的文献11篇，涉及rs699947(C/A)多态性的文献7篇，涉及rs3025039(C/T)多态性的文献8篇。入选文献无明显偏倚，各文献异质性检验显示rs699947、rs3025039研究结果无显著异质性（P=0.56，I2=0%；P=0.18，I2=31%）；rs1570360（P=0.01，I2=67%）入选文献存在显著异质性。Meta分析显示rs1570360、rs699947与RSA无明显相关性，合并OR及95%可信区间分别为1.16(0.96-1.41)、1.01(0.78-1.30)；rs3025039与RSA有一定的相关性，合并OR及95%可信区间为1.33(1.11-1.60)，P0.05。本次研究根据所收集资料的特点，对不同影响因素进行了敏感性分析，分析结果与原结果相似，支持总样本研究结果。结论VEGF基因rs1570360、rs699947多态性与复发性自然流产（RSA）无明显相关性，VEGF基因rs3025039多态性与复发性自然流产（RSA）存在一定的相关性。敏感性分析和发表性偏倚的识别结果表明，本次Meta分析结果稳定、可靠，反映了近十年来VEGF基因rs1570360、rs699947、rs3025039与RSA关系的研究结果。
[Abstract]:The purpose of this study is to investigate the expression of vascular endothelial growth factor (vascular endothelial, growth factor, VEGF) gene rs699947 (C/A), rs1570360 (G/A), rs833061 (T/C) and rs3025039 (C/T) four polymorphic loci and the Han nationality women in Ningxia area Chinese recurrent natural runoff (recurrent spontaneous abortion, RSA) and the correlation. Correlation analysis between four SNP loci of VEGF gene constructed haplotype and recurrent spontaneous abortion.
Methods 203 cases of recurrent spontaneous abortion patients from January 2006 to July 2009 for chromosome examination in Ningxia Medical University were selected in the laboratory of reproductive and genetic group, age 19-42 years, mean age 27.63 + 4.44; control group were matched with the case group age from January 2008 to October 2010 in Yinchuan Maternal and Child Health-Care Center of normal pregnant women in 190 cases, age 20-36 years old. The average age of 27.26 + 2.31 years. Using polymerase chain reaction restriction fragment length polymorphism (polymerase chain-reaction restricted fragment length polymorphism, PCR-RFLP) and allele specific PCR (AS-PCR) group and control group cases detection VEGF gene four polymorphism. Chi square test and estimate the relative risk of disease using SPSS18.0 statistical software to calculate and compare the frequency of each genotype, allele frequency, odds ratio (OR) and 95% confidence Interval (95%CI), we analyzed the correlation between four SNPs loci of VEGF gene and recurrent spontaneous abortion. We used Haploview software to conduct linkage disequilibrium and haplotype analysis, and to explore the association between the four SNPs loci of VEGF gene and the susceptibility of recurrent spontaneous abortion.
The results of genetic equilibrium test, VEGF gene four polymorphism loci except for rs1570360, other sites of the genotype distribution was in accordance with Hardy-Weinberg law of balance, with a representative group. The VEGF gene rs833061 genotype and allele frequency distribution in the case group and control group were compared, the results showed that there were statistically significant differences (P0.001).VEGF gene rs3025039 genotype and allele frequency distribution in the case group and control group were compared, the results showed that there were statistically significant differences (P0.01). The VEGF gene rs699947, rs1570360 locus genotype distribution and allele frequencies in the case group and control group. There was no statistical significance (P0.05). The VEGF gene of rs699947, rs833061 and rs3025039 three locus haplotypes were constructed in 5 kinds of protective haplotypes in the case group and the control group. There were statistical significance (P0.05, OR1); the distribution of 5 types of risk haplotypes in the two groups was statistically different (P0.05, OR1).
Conclusion 1. VEGF gene rs699947, the susceptibility of rs1570360 polymorphism in Ningxia Han women with recurrent spontaneous abortion is independent of.2, VEGF gene rs833061, rs3025039 gene polymorphism is associated with the recurrent spontaneous abortion, genotypes carrying rs833061T and rs3025039T alleles may be the susceptible women of Han nationality in Ningxia recurrent spontaneous abortion factors.3, VEGF gene haplotypes, 5 haplotypes may be a protective factor in Ningxia Han women with recurrent spontaneous abortion, 5 haplotypes may be a risk factor in Ningxia Han nationality women with recurrent spontaneous abortion.
Objective to evaluate and integrate the existing data on the study of the association of VEGF gene polymorphism with recurrent spontaneous abortion.
A case-control study on the association between VEGF gene polymorphism and recurrent spontaneous abortion through the methods of literature retrieval collection of databases at home and abroad since the open library to published in November 2013, does not conform to the requirements of the literature, using RevMan5.2 software, based on the heterogeneity test, analysis of fixed effect model and random effect model of Meta. Different inclusion criteria were used to evaluate the sensitivity analysis, funnel plot of publication bias.
The results included in standard 11 were published and unpublished literature 1 (this study), including rs1570360 (G/A) polymorphism in 11 literatures related to rs699947 (C/A) polymorphism in 7 literatures related to rs3025039 (C/T) polymorphism in 8 literatures. The selected literature had no obvious bias. The results of heterogeneity test showed that rs699947, no significant heterogeneity of the results of rs3025039 (P=0.56, I2=0%; P=0.18, I2=31%); rs1570360 (P=0.01, I2=67%) significant heterogeneity in.Meta analysis showed that rs1570360 existed in the literature, rs699947 and RSA had no significant correlation with OR, and 95% confidence intervals were 1.16 (0.96-1.41). 1.01 (0.78-1.30); there is a certain correlation between rs3025039 and RSA, combined with OR and 95% with 1.33 confidence intervals (1.11-1.60), P0.05. of the study according to the characteristics of data, the effect of different factors in the sensitivity analysis, the results were similar with the original, Support the results of the total sample study.
Conclusion VEGF gene rs1570360, rs699947 polymorphism and recurrent spontaneous abortion (RSA) there is no significant correlation between VEGF gene rs3025039 polymorphism and recurrent spontaneous abortion (RSA). There is a correlation between the sensitivity analysis and publication bias in the recognition results show that the Meta analysis results are stable and reliable, reflects the past ten years VEGF gene rs1570360, rs699947, rs3025039 and RSA between the results.

【学位授予单位】：宁夏医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R714.21

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