CYP17基因多态性与复发性自然流产（RSA）的关联性研究

发布时间：2018-01-15 03:02

本文关键词：CYP17基因多态性与复发性自然流产（RSA）的关联性研究　出处：《宁夏医科大学》2014年硕士论文　论文类型：学位论文

【摘要】：目的本研究对细胞色素氧化酶P450c17a（cytochrome P450c17a，CYP17）基因的rs743572（T/C）, rs6162（C/T）, rs6163（G/T）三个多态性位点进行检测，探讨CYP17基因三个多态性位点及其单倍型与宁夏汉族复发性自然流产（RSA）的相关性。方法病例组选取2009年1月-2011年12月在宁夏医科大学生殖与遗传重点实验室进行染色体检查的复发性自然流产患者160例；对照组选取与病例组年龄等相匹配的2009年1月-2011年12月在宁夏银川市妇幼保健院正常分娩的女性169例。采用聚合酶链反应（polymerase chain reaction, PCR）技术对病例组与对照组的目的片段进行扩增，通过焦磷酸测序技术（pyrosequencing）对CYP17基因扩增片段中的三个多态性位点进行基因分型。用SPSS16.0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CYP17基因三个SNPs位点与复发性自然流产的相关性，用Haploview软件进行单倍型构建来探讨CYP17基因的三个SNPs位点与复发性自然流产的易感性是否有关联。结果1、经遗传平衡定律检验，CYP17基因三个多态性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。2、CYP17基因rs743572（T/C）、rs6162（C/T）、和rs6163三个多态性位点基因型和等位基因频率在病例组与对照组中的分布频率差异均无统计学意义（P0.05）；三个位点的隐性基因模型和显性基因模型在病例组与对照组中的分布频率显著性差异不明显（P0.05）。3、CYP17基因三个SNPs位点之间，rs743572和rs6162、rs6162和rs6163、rs743572和rs6163之间为高度连锁不平衡（D’0.7）。4、CYP17基因rs743572、rs6162和rs6163三个单核苷酸多态性位点相互构建的单倍型共18种，其中频率大于0.03的有8种（A-C、G-T、T-T、G-C、T-C、C-T、T-T-C、G-C-T）。rs6163、rs6162、rs743572三个多态性位点两两构建的单倍型中：各单倍型频率在病例组与对照组中的差异无统计学意义(P0.05)；三个多态性位点rs6163-rs6162-rs743572构建的单倍型数据显示：各单倍型频率在病例组与对照组中的差异无统计学意义(P0.05)。结论1、CYP17基因rs743572、rs6162、rs6163三个多态性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，可能与宁夏汉族女性复发性自然流产的易感性无关。2、CYP17基因三个SNPs位点两两之间存在高度连锁不平衡。3、CYP17基因构建的单倍型中，各单倍型在病例组与对照组中的分布均无统计学意义，可能与宁夏汉族女性复发性自然流产的易感性无关。目的探讨CYP17基因rs743572T→C单核苷酸多态性位点与复发性自然流产易感性之间是否存在相关性。方法检索PubMed、中国生物医学文献数据库(CBM)、相关期刊论文(CNKI)、等数据库。检索国内外公开发表的CYP17基因rs743572（T→C）单核苷酸多态性位点与复发性自然流产易感性关系的研究。以病例组及对照组CYP17基因（T→C）等位基因分布的比值比(OR)为效应指标，，应用Review Manager5.2统计软件根据异质性检验结果选择随机效应模型或固定效应模型对OR进行合并分析，对不同纳入标准的结果进行敏感性分析，用漏斗图评估发表性偏倚。结果最终纳入分析文献6篇，病例组745例，对照组756例。显性模式下:以野生纯合子TT为参照评估突变纯合子和杂合子(CC+TC)患复发性自然流产的风险，异质性检验结果显示Pheterogeneity=0.01，存在显著异质性，故采用随机效应模型进行合并，Meta分析结果显示：突变纯合子和杂合子(CC+TC)在病例组和对照组中无显著差异性（OR=1.42，95%CI=0.96-2.10，Z=1.75，P=0.08）；隐形模式下:以野生纯合子和杂合子(TT+TC)为参照评估突变纯合子CC患复发性自然流产的风险，异质性检验结果显示Pheterogeneity=0.009，存在显著异质性，故采用随机效应模型进行合并，Meta分析结果显示：突变纯合子CC基因型在病例组和对照组中无显著差异性（OR=0.95，95%CI=0.60-1.53，Z=0.19P=0.85）。结论CYP17基因rs743572（T→C）单核苷酸多态性位点与复发性自然流产易感性无关联。
[Abstract]:The purpose of this study on cytochrome oxidase P450c17a (cytochrome P450c17a CYP17) gene rs743572 (T/C), rs6162 (C/T), rs6163 (G/T) three polymorphic loci were detected on three CYP17 gene polymorphisms and haplotypes in Ningxia Han and recurrent spontaneous abortion (RSA) correlation.
Methods 160 cases of patients with recurrent spontaneous abortion in January 2009 -2011 years in December for chromosome examination in Ningxia Medical University Key Laboratory of reproduction and genetics in the patients group; control group selected matched age in January 2009 -2011 year in December in Ningxia Yinchuan Maternal and Child Health-Care Center of normal pregnant women in 169 cases. Polymerase chain reaction (polymerase chain reaction, PCR) fragment of case group and control group were amplified by pyrosequencing (pyrosequencing) of three polymorphic sites in the amplified CYP17 gene fragment were genotyped. Chi square test and disease relative risk estimation using the SPSS16.0 statistical software to calculate and compare the frequency of each genotype. The allele frequencies, the odds ratio (OR) and 95% confidence intervals (95%CI), analysis of the CYP17 gene of three SNPs loci and recurrent spontaneous abortion The correlation of the three SNPs loci of the CYP17 gene is associated with the susceptibility to recurrent spontaneous abortion by using the haplotype of the Haploview software.
The 1, the law of genetic equilibrium test, CYP17 gene of three polymorphic loci and the genotype distribution was in accordance with Hardy-Weinberg law of balance, with a representative group of.2, CYP17 gene rs743572 (T/C), rs6162 (C/T), and the difference in the frequency distribution of rs6163 three polymorphic loci genotype and allele frequencies in the case group and control group were not statistically significant (P0.05); the frequency distribution of recessive gene model and dominant gene model three loci in the case group and control group was no significant difference between.3 (P0.05), three SNPs loci of CYP17 gene, rs743572 and rs6162, rs6162 and rs6163, between rs743572 and rs6163 is a high linkage disequilibrium (D 0.7).4, CYP17 gene rs743572, rs6162 and rs6163 three single nucleotide polymorphisms between the haplotypes were constructed 18 kinds, the frequency is more than 0.03 8 (A-C, G-T, T-T, G-C, T-C, C-T, T-T-C, .rs6163, rs6162, G-C-T) rs743572 three polymorphic loci and 22 haplotypes were constructed: there was no significant difference in the haplotype frequencies in the case group and in the control group (P0.05); haplotype data of three polymorphic loci constructed by rs6163-rs6162-rs743572 showed that there was no significant difference in the haplotypic frequency in case group and control group in (P0.05).
Conclusion 1. CYP17 gene rs743572, rs6162, rs6163 distribution of three polymorphic loci genotypes and allele frequencies in the case group and control group were not statistically significant, probably with susceptibility to recurrent spontaneous abortion women of Han nationality in Ningxia is independent of the.2, there are high linkage disequilibrium between.3 gene CYP17 three SNPs 22 loci, CYP17 gene haplotype, haplotype distribution in the case group and control group were not statistically significant, probably has nothing to do with susceptibility to Ningxia Han women with recurrent spontaneous abortion.
Objective to investigate whether there is a correlation between the single nucleotide polymorphisms of the CYP17 gene rs743572T to C and the susceptibility to recurrent spontaneous abortion.
Method to retrieve the PubMed, Chinese biomedical literature database (CBM), China Journal Full-text Database (CNKI), such as database. The retrieval of CYP17 rs743572 gene published at home and abroad (T, C) of single nucleotide polymorphism and susceptibility to recurrent spontaneous abortion. In case group and control group CYP17 gene (T, C) the allele distribution ratio (OR) as effect indicators, using Review Manager5.2 software according to the heterogeneity test results of random effect model and fixed effect model combined with analysis of OR of different inclusion standard sensitivity analysis results, using funnel plots assessment of publication bias.
Results in the final analysis of 6 articles, 745 cases, 756 cases in the control group. The dominant mode: Nobu Juriko TT as the reference evaluation of mutant homozygous and heterozygous (CC+TC) risk of recurrent spontaneous abortion, heterogeneity test showed that Pheterogeneity=0.01 had significant heterogeneity, the random effect model combined with. Meta analysis showed that the mutant homozygous and heterozygous (CC+TC) in the case group and the control group had no significant difference (OR=1.42,95%CI=0.96-2.10, Z=1.75, P=0.08); stealth mode: Nobu Juriko and heterozygous (TT+TC) as the reference evaluation of homozygous CC mutation patients with recurrent spontaneous abortion risk heterogeneity test showed that Pheterogeneity=0.009 therefore, there is significant heterogeneity, the random effects model with the results of Meta analysis showed that the homozygous CC mutation genotype in the case group and control group There was no significant difference (OR=0.95,95%CI=0.60-1.53, Z=0.19P=0.85).
Conclusion the single nucleotide polymorphisms of the CYP17 gene rs743572 (T to C) are not associated with the susceptibility to recurrent spontaneous abortion.

【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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