炎症相关基因多态性与复发性流产的相关性研究

发布时间：2018-04-29 18:41

本文选题：基因多态性 + 复发性流产　；参考：《天津医科大学》2017年硕士论文

【摘要】：目的:本研究的主要目的在于探讨炎症相关基因多态性与不明原因复发性流产易感性之间的关系。炎症相关候选基因包括FOXP3 rs2232365,CTLA4 rs231775,CX3CR1 rs3732378,CX3CR1 rs3732379,FAU rs769440,IL-21 rs13143866,CCR5rs1799987,IL-18 rs360718。方法:本研究的病例组选自2014.09至2016.11期间就诊于天津医科大学第二医院计划生育科不孕不育门诊的107例连续2次及2次以上不明原因的复发性流产患者,年龄20-40岁,平均年龄28.50±3.67岁。对照组为同期就诊于天津医科大学第二医院计划生育科流产门诊的187例健康育龄女性,年龄20-40岁,平均年龄28.18±3.72岁。通过采用PCR产物扩增后的DNA直接测序的试验方法对FAU rs769440位点进行基因分型,采用Sequenom Mass ARRAY@分子量阵列技术对其他各个候选基因位点进行基因分型;Hardy-Weinberg平衡、基因型鉴定、等位基因频率的比较及比值比(odd ratio,OR)和95%值信区间计算采用在线软件SHEsis的卡方检验完成;连锁不平衡的统计学分析是采用Haploview(Ver.3.32)软件,并进行D’和r2的计算;采用UNPHASE系统进行单倍体型分布的分析;采用Quanto软件进行检验效能分析。统计结果p0.05有统计学意义。结果:(1)对复发性流产病例组和健康育龄妇女对照组的炎症相关候选基因多态位点的基因型频率分布分别进行检测,结果提示均符合Hardy-Weinberg平衡法则(P0.05),已达到了遗传平衡,说明所选取的样本具有群体代表性;(2)FAU rs769440 C/G等位基因分布频率在病例组-对照组分别为129/85和242/135,两组结果进行比较发现其差异具有统计学意义(P=0.019)。(3)对其他候选基因位点的多态性,将复发性流产病例组与健康育龄妇女对照组的等位基因分布频率进行比较,发现两组间的差异无明显统计学意义,FOXP3rs2232365(A/G,P=0.968),CTLA4 rs231775(A/G,P=0.533),CX3CR1 rs3732378(A/G,P=0.716),CX3CR1 rs3732379(C/T,P=0.73),IL-21 rs13143866(A/G,P=0.266),CCR5 rs1799987(C/T,P=0.593)and IL-18 rs360718(A/G,P=0.966)。(4)对候选基因多态位点进行连锁不平衡分析,FOXP3 rs2232365,CTLA4rs231775,CX3CR1 rs3732378,CX3CR1 rs3732379和FAU rs769440两两之间D’值的范围在0.98-1,r2值范围在在0-1之间。(5)对FOXP3 rs2232365,CTLA4 rs231775,CX3CR1 rs3732378,CX3CR1rs3732379和FAU rs769440进行单倍体型分析,数据显示无统计学意义(P0.05)。结论:(1)在中国京津冀地区汉族人群中,FAU rs769440的多态性与复发性流产易感性相关。(2)FOXP3 rs2232365,CTLA4 rs231775,CX3CR1 rs3732378,CX3CR1rs3732379,IL-21 rs13143866,CCR5 rs1799987,IL-18 rs360718基因多态性与复发性流产的易感性无关
[Abstract]:Objective: the main purpose of this study is to explore the relationship between inflammation related gene polymorphism and the susceptibility to unexplained recurrent spontaneous abortion. The candidate genes for inflammation include FOXP3 rs2232365, CTLA4 rs231775, CX3CR1 rs3732378, CX3CR1 rs3732379, FAU rs769440, IL-21 rs13143866. The case group was selected from 2014.09 to 2016.11 in the sterile clinic of the family planning department of the Second Hospital Affiliated to Tianjin Medical University from 2014.09 to 2016.11. The patients with 2 and more than 2 times of unexplained recurrent abortion were aged 20-40 years old, with an average age of 28.50 + 3.67 years. The control group was diagnosed with abortion in family planning department of the hospital in the same period. 187 healthy women of child-bearing age in the outpatient clinic, aged 20-40 years, with an average age of 28.18 + 3.72 years, were genotyping for FAU rs769440 loci by direct sequencing of DNA after amplification of PCR products. The Sequenom Mass ARRAY@ molecular weight array technique was used to genotyping other candidate gene loci; Hardy-Weinberg balance, Genotype identification, comparison of allele frequencies and the ratio Ratio (odd ratio, OR) and 95% value letter interval calculation were completed by the chi square test of online software SHEsis; the statistical analysis of linkage disequilibrium was using Haploview (Ver.3.32) software, and the calculation of D 'and R2; using UNPHASE system for the analysis of the haplotype distribution; using Quant. O software performed the test effectiveness analysis. The statistical results P0.05 had statistical significance. Results: (1) the genotype frequency distribution of the polymorphic loci of the inflammatory candidate genes in the recurrent abortion cases and the healthy childbearing age women was detected respectively. The results suggested that the Hardy-Weinberg balance rule (P0.05) was consistent with the genetic balance. The selected samples were representative of the group; (2) the frequency of FAU rs769440 C/G allele distribution was 129/85 and 242/135 in the case group and the control group respectively. The difference between the two groups was statistically significant (P=0.019). (3) the polymorphism of the other candidate gene loci, the recurrent abortion case group and the healthy childbearing age women were used. FOXP3rs2232365 (A/G, P=0.968), CTLA4 rs231775 (A/G, P=0.533), CX3CR1 rs3732378 (A/G, P=0.716). 6) (4) linkage disequilibrium analysis of polymorphic loci of candidate genes, the range of D 'value between FOXP3 rs2232365, CTLA4rs231775, CX3CR1 rs3732378, CX3CR1 rs3732379 and FAU rs769440 22 is 0.98-1, R2 values range from 0-1. The data of ploidy analysis showed no statistical significance (P0.05). Conclusion: (1) the polymorphism of FAU rs769440 was associated with the susceptibility to recurrent spontaneous abortion among the Han population in Beijing Tianjin Hebei region. (2) FOXP3 rs2232365, CTLA4 rs231775, CX3CR1 rs3732378, CX3CR1rs3732379, IL-21 rs13143866, and relapse The susceptibility of sexual abortion is unrelated

【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R714.21

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