UCP2基因多态性与神经管畸形关系的研究

发布时间：2018-11-09 13:24

【摘要】： 目的:寻找山西省神经管畸形(neural tube defects, NTDs)高发的可疑危险因素(包括遗传、环境及营养等方面),探讨母亲线粒体膜转运蛋白UCP2(uncoupling proteins-2,UCP2 )基因和子代发生NTDs风险性之间的关系,并研究危险因素间是否存在交互作用,从而揭示多因素在NTDs发生中的作用。方法:选取2003年3月至2005年10月间在山西省6个高发地区的25所医院生育NTDs患儿或B超诊断为NTDs患儿而引产的母亲116例为病例组,选取同期生育正常儿的母亲或与病例组孕周相近的孕妇116名为对照组,进行1:1配比的病例对照研究。对两组对象进行问卷调查,同时,对每一个调查对象抽取肘静脉血2 ml,提取DNA,采用聚合酶链反应—限制性片段长度多态性(polymerase chain reaction-restriction fragment length polymorphism analysis, PCR—RFLP)方法检测调查对象UCP2基因第8外显子3'非编码区45bp碱基的缺失或插入和第4外显子的55位点多态性。采用SPSS 11.0软件进行统计学分析,比较病例组和对照组基因频率分布,并结合环境因素进行单因素、多因素及交互作用分析。结果:(1)UCP2基因第8外显子3'非编码区45bp碱基的缺失或插入的基因频率在病例组和对照组的比较:UCP2基因第8外显子3'非编码区45bp碱基的缺失或插入在此次研究中有三种基因型,即D/D、D/I和I/I。其基因型频率(D/D、D/I、I/I)在病例组的构成分别为87.9%、11.2%、和0.9%,在对照组的构成分别为69.0%、24.1%、和6.9%。两组间差异有统计学意义(χ2=8.34,P0.05);其等位基因频率(D、I)在病例组的分布为93.5%和6.5%,在对照组的分布为81.0%和19.0%,两组间差异有统计学意义(χ2=16.33,P0.01)。而且基因型中随着D等位基因的增加,母亲生育NTDs患儿的可能性逐渐增加(趋势χ2=97.71,P0.001)。山西汉族人群UCP2基因3’非编码区45bp碱基的缺失或插入基因型分布与美国加利福尼亚人之间差异有统计学意义(P0.05),而与大连、上海之间差异无统计学意义(P0.05)。等位基因频率分布与上海和美国加利福尼亚人之间差异有统计学意义(P0.05),而与大连之间差异无统计学意义(P0.05)。 (2)UCP2基因第4外显子的55位点的基因频率在病例组和对照组的比较:UCP2基因55位点有2种基因型,即野生型AA、杂合突变型AV。其基因型频率(AA、AV)在病例组的分布为33.6%、66.4%,在对照组的分布为25.0%、75.0%,两组间差异无统计学意义(χ2=2.08,P0.05);其等位基因频率(A、V)在病例组的分布为66.8%和33.2%,在对照组的分布为62.5%和37.5%,两组间差异无统计学意义(χ2=0.943,P0.05)。 (3)可疑危险因素单、多因素分析:经单因素配对条件Logistic回归分析有统计学意义的变量16项引入多因素配对条件Logistic回归分析,最终进入模型的变量有4项。分别
[Abstract]:Objective: to explore the suspicious risk factors (including heredity, environment and nutrition) of high incidence of (neural tube defects, NTDs) in neurotubule malformation in Shanxi Province, and to explore the maternal mitochondrial membrane transporter UCP2 (uncoupling proteins-2,). The relationship between UCP2) gene and the risk of NTDs in offspring, and the study of the interaction between risk factors, so as to reveal the role of multiple factors in the pathogenesis of NTDs. Methods: from March 2003 to October 2005, 116 mothers with NTDs or NTDs diagnosed by B-ultrasound in 25 hospitals in 6 high incidence areas of Shanxi Province were selected as the case group. A 1:1 matched case-control study was carried out on 116 mothers with normal birth at the same time or pregnant women of similar gestational weeks in the case group. Two groups of subjects were investigated by questionnaire. At the same time, 2 ml, of cubital vein blood was extracted from each of them by polymerase chain reaction-restriction fragment length polymorphism (polymerase chain reaction-restriction fragment length polymorphism analysis,). PCR-RFLP) was used to detect the deletion or insertion of the 45bp base in exon 8 of the UCP2 gene and the 55 locus polymorphism in exon 4 of the UCP2 gene. SPSS 11.0 software was used to analyze the gene frequency distribution in case group and control group, and univariate, multi-factor and interaction analysis were carried out in combination with environmental factors. Results: (1) the frequency of deletion or insertion of 45bp base in exon 8 of UCP2 gene was compared with that of control group. The deletion or insertion of 45bp base in exon 8 of UCP2 gene was compared with that in control group. There were three genotypes in this study. That's D / D, D / R, I, I, Its genotype frequency (D / I / I) was 87.9 and 0.9 in the case group, and 69.0 and 6.9 in the control group, respectively. The difference between the two groups was statistically significant (蠂 2 = 8.34 P 0.05). The allelic frequencies (DNI) were 93.5% and 6.5% in the case group and 81.0% and 19.0 in the control group, respectively. The difference between the two groups was statistically significant (蠂 ~ 2 = 16.33, P 0.01). Moreover, with the increase of D allele in genotype, the possibility of mother to bear NTDs increased gradually (trend 蠂 2: 97.71 / P0.001). The genotype distribution of 45bp gene deletion or insertion in the 3'non-coding region of UCP2 gene in Shanxi Han population was significantly different from that in California (P0.05), but not between Dalian and Shanghai (P0.05). The allele frequency distribution was significantly higher than that between Shanghai and California (P0.05), but not between Dalian and Dalian (P0.05). (2) comparison of gene frequency of 55 locus in exon 4 of UCP2 gene between case group and control group: there are two genotypes of UCP2 gene 55 locus, that is, wild-type AA, heterozygous AV.. The distribution of genotype frequency (AA,AV) was 33.66.4in the case group and 25.0 / 75.0in the control group. There was no significant difference between the two groups (蠂 ~ (2 +) 2.08). The allelic frequencies (AV) were 66.8% and 33.2% in the case group and 62.5% and 37.5% in the control group, respectively. There was no significant difference between the two groups (蠂 2 / 0.943 P 0.05). (3) suspicious risk factor single, multivariate analysis: by univariate paired conditional Logistic regression analysis, 16 variables with statistical significance were introduced multivariate paired conditional Logistic regression analysis, and finally 4 variables entered the model. Separate
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2006
【分类号】：R394

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