本文關(guān)鍵詞：復發(fā)性流產(chǎn)遺傳學病因研究及凝血因子V Leiden突變與復發(fā)性流產(chǎn)關(guān)系研究的Meta分析　出處：《華中科技大學》2014年博士論文　論文類型：學位論文

  更多相關(guān)文章： 復發(fā)性流產(chǎn) 染色體 單核苷酸多態(tài)性 微陣列分析 復發(fā)性流產(chǎn) 易栓癥 凝血因子V Leiden

【摘要】：目的：探討RPL的遺傳學病因,以及SNP-array技術(shù)在RPL患者遺傳學病因診斷中的應用。 材料和方法：收集2012年1月-2014年1月因復發(fā)性流產(chǎn)就診于我院生殖中心門診及入住計劃生育病房患者的流產(chǎn)組織,使用SNP-array對流產(chǎn)組織進行分析,從而發(fā)現(xiàn)導致RPL的病因。 結(jié)果：共對10例RPL患者的流產(chǎn)組織使用SNP-array進行染色體分析,2例(20%)未見明顯異常,8例(80%)有異常。異常染色體中,5例為染色體三體(1例為2號染色體三體,1例為13號染色體3體,1例為21號染色體三體,2例為22號染色體三體),占染色體異常的總?cè)藬?shù)的62.5%,5例為染色體結(jié)構(gòu)異常(包括3例片段缺失及2例單親二倍體)占染色體異�？�?cè)藬?shù)的62.5%,同時具有染色體數(shù)目和結(jié)構(gòu)異常的有2例(1例為22號染色體三體及11號染色體雜合性缺失,1例為13號染色體三體及10號染色體微小片段缺失),占染色體異常總?cè)藬?shù)的25%。 結(jié)論：染色體異常是導致RPL的常見原因,在各種染色體異常中以染色體的多體性改變最為常見,單核苷酸多態(tài)性微陣列技術(shù)以其高檢出率及高分辨率的優(yōu)勢為復發(fā)性流產(chǎn)遺傳學病因的診斷提供了更好的方法。 目的：探討凝血因子V Leiden突變與復發(fā)性流產(chǎn)的關(guān)系。 方法：在PubMed, Embase,萬方,維普等中外文數(shù)據(jù)庫中,檢索研究凝血因子VLeiden突變與復發(fā)性流產(chǎn)關(guān)系的文獻。由兩位獨立的研究人員根據(jù)納入標準和排除標準對獲得的文獻進行篩選,完成篩選后進行數(shù)據(jù)的提取,將提取的數(shù)據(jù)信息錄入事先設計好的標準化表格中,最終使用RevMan5.2軟件對納入的文獻進行Meta分析。 結(jié)果：最終納入21篇文獻,在總體分析中,無論是FVLG1691AGA基因型、純AA基因型、GA+AA基因型還是A等位基因頻率,病例組導致復發(fā)性流產(chǎn)的風險均高于對照組,且有統(tǒng)計學意義,OR值分別為2.12(95%CI,1.70-2.64; P 0.00001),5.59(95%CI,1.84-16.96; P=0.002),1.84(95%CI,1.34-2.54; P=0.0002),1.79(95%CI,24-2.59). 在亞組分析中,針對人種進行的分析時,在高加索人種中,FVLG1691AGA基因型、GA+AA基因型、A等位基因頻率病例組導致復發(fā)性流產(chǎn)的風險均比對照組高,且有統(tǒng)計學意義,OR值分別為1.98(95%CI,1.51-2.60; P0.0001),1.75(95%CI,1.22-2.49; P0.002)1.70(95%CI,1.12-2.57; P=0.01); FVLG1691A AA基因型與RPL也有關(guān),但沒有統(tǒng)計學意義,OR3.26(95%CI,0.95-11.18; P=0.06)。在對混合人種進行的FVL G1691A GA基因型、GA+AA基因型分析中,病例組導致復發(fā)性流產(chǎn)的風險均較對照組高,OR值分別為2.40(95%CI,1.64-3.52; P0.00001),2.71(95%CI,1.86-3.95; P0.00001);該亞組有一篇文獻對FVL G1691A AA基因型進行檢測OR87(95%CI,12-627;P0.001); FVLG1691AGA+AA基因型與RPL相關(guān),但沒有統(tǒng)計學意義,OR1.97(95%CI,0.97-4.00; P=0.06)。在不同妊娠時期流產(chǎn)的分析中,妊娠早期的研究中,FVL G1691AGA基因型、AA基因型、GA+AA基因型以及A等位基因頻率,病例組較對照組均與復發(fā)性流產(chǎn)的關(guān)系明顯,OR值分別為1.77(95%CI,1.18-2.65; P=0.006),9.51(95%CI,2.23-40.56; P=0.002),1.79(95%CI,1.13-2.86;P=0.001),1.71(95%CI,1.05-2.79; P=0.03)。對妊娠中期流產(chǎn),FVLG1691AGA基因型、GA+AA基因型及A等位基因頻率,病例組導致復發(fā)性流產(chǎn)的風險均較對照組高,且都具有統(tǒng)計學意義,OR值分別為4.91(95%CI,3.24-7.45; P0.00001),5.81(95%CI,3.85-8.74; P0.0001),3.83(95%CI,1.92-7.62; P=0.0001),該亞組有一篇文獻對FVL G1691AAA基因型進行分析,OR168(95%CI,22-879;P0.0001)。 結(jié)論：從本meta分析結(jié)果來看,FVL與RPL有較強的關(guān)系,該突變GA基因型導致復發(fā)性流產(chǎn)的風險為正常人的2倍,AA基因型則可達5.6倍,攜帶A等位基因?qū)е聫桶l(fā)性流產(chǎn)風險為正常人的2倍。同時我們發(fā)現(xiàn)該突變存在人種的遺傳異質(zhì)性,高加索人種和混合人種中該突變與RPL均相關(guān),混合人種攜帶FVL導致復發(fā)性流產(chǎn)的幾率更高。在早期和中期妊娠中,FVL均可導致復發(fā)性流產(chǎn),且在中期流產(chǎn)的危險性更高。由于RPL是一種多因素共同作用的疾病,需要更多研究來對其病因進行探究。
[Abstract]:Objective: To investigate the genetic causes of RPL and the application of SNP-array in the genetic diagnosis of RPL patients.
Materials and methods: We collected the aborted tissues from the reproductive center clinic and the family planning ward in January 2012 -2014 January, and analyzed the abortion tissues by SNP-array, and found the cause of RPL.
Results: a total of abortion tissue of 10 cases with RPL chromosome analysis using SNP-array, 2 cases (20%) had no obvious abnormalities, 8 cases (80%) had abnormal chromosome abnormalities. In 5 cases (1 cases of trisomy trisomy of chromosome 2, 1 cases of chromosome 13, 3, 1 cases trisomy of chromosome 21, 2 cases of trisomy 22), the total number of chromosome abnormalities in 62.5%, 5 cases of chromosome structural abnormalities (including 3 cases of deletion and 2 cases of uniparental disomy) accounted for 62.5% of the total number of chromosomal abnormalities, and chromosome number and structural abnormality in 2 cases (1 cases trisomy of chromosome 22 and chromosome 11 LOH, 1 cases of trisomy 13 and loss of chromosome 10, chromosome abnormalities accounted for tiny fragments) the total number of 25%.
Conclusion: chromosomal abnormalities are common causes of RPL, in a variety of chromosomal abnormalities in chromosome polysomy change is most common, single nucleotide polymorphism microarray technology to the diagnosis of high detection rate and high resolution advantages for recurrent spontaneous abortion etiology provides a better way.
Objective: To investigate the relationship between the mutation of coagulation factor V Leiden and recurrent abortion.
Methods: PubMed, Embase, Wanfang, VIP and other foreign language database, retrieval of coagulation factor VLeiden mutation and recurrent abortion relation literature. By two independent researchers according to inclusion criteria and exclusion criteria of the literature screening, completed after screening the data extraction, data entry information extraction the advance design standard form in the final, RevMan5.2 software was used for Meta analysis of included literature.
Results: a total of 21 articles in the overall analysis, both the FVLG1691AGA genotype, pure AA genotype, GA+AA genotype and A allele frequency, resulting in the risk of recurrent spontaneous abortion cases were higher than the control group, and there was statistical significance, OR values were 2.12 (95% CI, 1.70-2.64; P 0.00001), 5.59 (95%CI, 1.84-16.96; P=0.002), 1.84 (95%CI, 1.34-2.54; P=0.0002), 1.79 (95%CI, 24-2.59).
In the subgroup analysis, according to the analysis of the race, in the Caucasian population, FVLG1691AGA genotype, GA+AA genotype and A allele frequency were risk of recurrent spontaneous abortion were higher than the control group, and there was statistical significance, OR values were 1.98 (95%CI, 1.51-2.60; P0.0001, 1.75) (95%CI, 1.22-2.49; P0.002) 1.70 (95%CI, 1.12-2.57; P=0.01; FVLG1691A) AA genotype and RPL, but no statistical significance (OR3.26, 95%CI, 0.95-11.18; P=0.06). In FVL G1691A GA based on a mixed race for type analysis of GA+AA genotype in case group, leading to the risk of recurrent abortion is higher than the control group, the OR values were 2.40 (95%CI, 1.64-3.52; P0.00001), 2.71 (95%CI, 1.86-3.95; P0.00001); the sub group has a review on FVL G1691A AA to detect OR87 genotype (95%CI, 12-627; P0.001); the FVLG1691AGA+AA genotype is associated with RPL, but no There was statistical significance (95%CI, OR1.97, 0.97-4.00; P=0.06). In the analysis of abortion during different stage of pregnancy in early pregnancy in the study, FVL G1691AGA genotype, AA genotype, GA+AA genotype and A allele frequency were compared with the control group were associated with recurrent spontaneous abortion, OR respectively. 1.77 (95%CI, 1.18-2.65; P=0.006), 9.51 (95%CI, 2.23-40.56; P=0.002), 1.79 (95%CI, 1.13-2.86; P=0.001), 1.71 (95%CI, 1.05-2.79; P=0.03). On the second trimester abortion, FVLG1691AGA genotype, GA+AA genotype and A allele frequencies, cases cause the risk of recurrent spontaneous abortion is higher than the control group, and have statistical significance, OR values were 4.91 (95%CI, 3.24-7.45; P0.00001), 5.81 (95%CI, 3.85-8.74; P0.0001), 3.83 (95%CI, 1.92-7.62; P=0.0001), the sub group has a literature analysis of FVL genotype G1691AAA, OR168 (95%CI, 22-879; P0.0001).
Conclusion: from the results of meta analysis, there is a strong relationship between FVL and RPL, the GA gene mutation type lead to 2 times the risk of recurrent spontaneous abortion for normal people, AA genotype is up to 5.6 times, the A allele leads to recurrent miscarriage risk is 2 times normal. At the same time, we found that the mutation and genetic heterogeneity in race, Caucasian and mixed races were related to the mutation and RPL, mixed race with FVL lead to the risk of recurrent miscarriage is higher. In the early and mid pregnancy, FVL can lead to recurrent spontaneous abortion, and in danger of second trimester abortion higher. Because RPL is a function of a a multi factor disease, more research is needed to explore its causes.

【學位授予單位】：華中科技大學
【學位級別】：博士
【學位授予年份】：2014
【分類號】：R714.21

【參考文獻】

相關(guān)期刊論文 前3條

1 馬淑芳;鄭梅玲;;MTHFRC677T基因多態(tài)性與復發(fā)性流產(chǎn)的關(guān)系[J];保健醫(yī)學研究與實踐;2008年04期

2 李剛;劉艷;孫瑩璞;;單核苷酸多態(tài)性微陣列在胚胎植入前遺傳學診斷中的應用[J];國際生殖健康/計劃生育雜志;2012年05期

3 劉宇巖;楊博逸;李永芳;盧響響;王達;孫貴范;;5,10-亞甲基四氫葉酸還原酶C677T基因多態(tài)性與原因不明復發(fā)性流產(chǎn)關(guān)聯(lián)的Meta分析[J];中國全科醫(yī)學;2013年31期

，

本文編號：1421414