基于单倍型的LBW易感基因多态性与维汉低出生体重儿的关联性分析

发布时间：2018-04-24 17:54

本文选题：低出生体重 + 微粒体环氧化物水解酶基因　；参考：《新疆医科大学》2017年硕士论文

【摘要】：目的:探讨微粒体环氧化物水解酶基因(EPHX1)、微小异源二聚体伙伴基因(SHP)、细胞色素氧化酶P4501A1基因(CYP1A1)和亚甲基四氢叶酸还原酶基因(MTHFR)多态性与乌鲁木齐市汉族和维吾尔族新生儿低出生体重(LBW)发生的关系。方法:采用病例对照研究方法,从新疆自治区人民医院及乌鲁木齐市妇幼保健院选取出生体重2500g的单胎足月新生儿96例作为病例组,出生体重2500g-4000g的单胎足月新生儿208例作为对照组,记录孕妇和新生一般情况,收集新生儿脐带血并提取DNA,采用wafergen高通量捕获平台二代测序技术检测EPHX1基因His139Arg和Ile181Ser位点、SHP的基因rs753658661和rs7504位点、CYP1A1基因的rs1048943和rs1799814位点、MTHFR基因rs1801133位点的基因多态性,对低出生体重组和正常组计数资料两组比较采用卡方检验,计量资料比较采用t检验,采用SHEsis在线软件进行Hardy-Weinberg平衡检验、连锁不平衡分析和单倍型分析;采用GMDR软件进行基因交互作用分析,确定最佳及交互作用模型;采用MDR软件画出基因交互作用放射图,判断其交互作用类型。结果:(1)对照组EPHX1、SHP、CYP1A1和MTHFR基因各SNP位点均服从Hardy-Weinberg平衡检验(P0.05)。(2)胎龄、孕妇年龄和新生儿性别构成比等一般情况在低出生体重组和对照组中差异无统计学意义(P0.05)。(3)EPHX1基因的His139Arg位点、SHP的基因rs753658661和rs7504位点、CYP1A1基因的rs1048943和rs1799814、MTHFR基因rs1801133位点与维吾尔族和汉族低出生体重发生无关(P0.05),EPHX1基因的Ile181Ser位点与维吾尔族低出生体重发生无关(P0.05),而与汉族低出生体重发生有关(P0.05),突变的TG杂合子基因型[OR=0.250(0.091-0.689)]和突变的G等位基因[OR=0.290(0.109-0.768)]可降低低出生体重发生危险性。(4)SHP基因的两个位点基因型组合和CYP1A1基因的两个位点基因型组合与维吾尔族和汉族低出生体重发生无关(P0.05),EPHX1基因的两个位点基因型组合与维吾尔族低出生体重发生无关(P0.05),而与汉族低出生体重发生有关(P0.05),与野生型AA/TT基因型组合比较,AA/TG基因型组合可降低低出生体重发生的危险性[OR=0.298(0.095-0.930)]。(5)维吾尔族和汉族EPHX1、SHP、CYP1A1基因上的多个位点在每个基因上均有一定强度的连锁不平衡,单倍型分析结果显示,SHP基因两个位点单倍型和CYP1A1基因单倍型与维吾尔族和汉族低出生体重发生无关,EPHX1基因两个位点单倍型与维吾尔族低出生体重发生无关(P0.05),而与汉族低出生体重发生有关(P0.05),A-G单倍型降低了低出生体重发生的危险性[OR=0.316(0.117-0.852)],G-T单倍型增高了低出生体重发生的危险性[OR=2.278(1.059-4.901)]。(6)GMDR和MDR软件分析可知,EPHX1基因的Ile181Ser位点和CYP1A1基因的rs1048943位点有拮抗作用(P0.05),由Ile181Ser位点突变的TG杂合子基因型和rs1048943位点突变的CC纯合子基因型组成的低危组低出生体重发生的危险性明显降低[OR=952.0(0.118-0.570),(P0.01)]。结论:(1)汉、维EPXH1、SHP、CYP1A1和MTHFR基因多态性对低出生体重的发生影响不一。(2)SHP、CYP1A1、MTHFR基因多态性与汉族和维吾尔族新生儿低出生体重无关,EPHX1基因Ile181Ser位点多态性与汉族新生儿低出生体重有关,而与维吾尔族新生儿低出生体重无关。(3)EPHX1基因的Ile181Ser位点和CYP1A1基因的rs1048943位点在低出生体重的发生中有拮抗作用。低出生体重的发生是多种基因联合作用引起的,故在今后的研究中,应尽可能纳入更多的基因综合分析,以期全面的了解低出生体重发生的遗传原因,从而为低出生体重的发生提供参考依据。
[Abstract]:Objective: To investigate the relationship between microsomal epoxide hydrolase gene (EPHX1), small heterologous two polymer partner gene (SHP), cytochrome oxidase P4501A1 gene (CYP1A1) and methylene tetramhydrofolate reductase gene (MTHFR) polymorphism with the incidence of low birth weight (LBW) in Urumqi Han and Uygur newborns. According to the study method, 96 single full-term newborns with birth weight 2500g were selected from the people's Hospital of Xinjiang autonomous region and the maternal and child health care hospital of Urumqi as a case group and 208 single full-term newborn babies born with a birth weight of 2500g-4000g as the control group. The general situation of pregnant women and newborn babies was recorded, the umbilical cord blood of the newborn was collected and DNA was extracted, and waferg was used. EN high throughput capture platform two generation sequencing technology detected the EPHX1 gene His139Arg and Ile181Ser loci, the SHP gene rs753658661 and rs7504 loci, the rs1048943 and rs1799814 loci of CYP1A1 gene, and the MTHFR gene rs1801133 locus gene polymorphism, and compared the chi square test to the low birth weight group and the normal group count data two groups. The material was compared with t test, using SHEsis online software for Hardy-Weinberg balance test, linkage disequilibrium analysis and haplotype analysis; GMDR software was used for gene interaction analysis to determine the best and interaction model; MDR software was used to draw gene interaction map to judge the type of interaction. (1) EP in control group. The SNP loci of HX1, SHP, CYP1A1 and MTHFR were all subject to Hardy-Weinberg balance test (P0.05). (2) the gestational age, the age of the pregnant women and the sex ratio of the newborn were not statistically significant (P0.05) in the low birth weight group and the control group (P0.05). (3) the His139Arg loci of the EPHX1 gene, the SHP gene rs753658661 and the locus of the gene. The rs1048943 and rs1799814, the rs1801133 locus of the MTHFR gene are not related to the uugur and Han people's birth weight (P0.05). The Ile181Ser locus of the EPHX1 gene is not related to the uugur birth weight (P0.05), but it is related to the low birth weight of the Han nationality (P0.05), the mutant TG heterozygote genotype [OR=0.250 (0.091-0.689)] and the mutation. The G allele [OR=0.290 (0.109-0.768)] could reduce the risk of low birth weight. (4) the combination of the two locus genotypes of the SHP gene and the combination of the two loci of the CYP1A1 gene were not related to the uugur and Han birth weight (P0.05), the genotype combination of the two loci of the EPHX1 gene and the low birth weight of the Uygur nationality P0.05 was related to the occurrence of low birth weight (P0.05). Compared with the wild type AA/TT genotype combination, the AA/TG genotype combination could reduce the risk [OR=0.298 (0.095-0.930) of the occurrence of low birth weight. (5) the multiple loci on EPHX1, SHP, and CYP1A1 genes in Uygur and Han nationality have a certain linkage in each gene. Unbalance, haplotype analysis showed that the haplotype of the two loci of the SHP gene and the haplotype of the CYP1A1 gene were not related to the low birth weight of the Uygur and Han nationality. The haplotype of the two loci of the EPHX1 gene was not related to the low birth weight of the Uygur nationality (P0.05), but it was related to the low birth weight of the Han nationality (P0.05), and the haplotype of the A-G was lower. The risk of birth weight [OR=0.316 (0.117-0.852)], G-T haplotype increased the risk of low birth weight (1.059-4.901). (6) GMDR and MDR software analysis showed that the Ile181Ser loci of the EPHX1 gene and rs1048943 loci of the CYP1A1 gene had antagonistic use (P0.05), and the heterozygote genotypes that were mutated by the loci. The risk of low birth weight generation in the low risk group composed of the CC homozygote genotypes of the rs1048943 loci was significantly reduced by [OR=952.0 (0.118-0.570), (P0.01). Conclusion: (1) Han, vitamin EPXH1, SHP, CYP1A1 and MTHFR gene polymorphisms have different effects on the occurrence of low birth weight. (2) SHP, CYP1A1, polymorphism of MTHFR genes and the Han and Uygur newborn The low birth weight of the EPHX1 gene is related to the low birth weight of the Han newborns and is not related to the low birth weight of the Uygur newborns. (3) the Ile181Ser locus of the EPHX1 gene and the rs1048943 locus of the CYP1A1 gene are antagonistic to the occurrence of low birth weight. The occurrence of low birth weight is a variety of genes. As a result of the combined effect, more genetic analysis should be included in future studies to provide a comprehensive understanding of the genetic causes of low birth weight and to provide a reference for the occurrence of low birth weight.

【学位授予单位】：新疆医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R722.1

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