四个单核苷酸多态性与非综合征性唇腭裂关系的Meta分析

发布时间：2018-04-12 18:54

本文选题：IRF6 + 8q24　；参考：《安徽医科大学》2015年硕士论文

【摘要】：目的近年来,有关唇腭裂的单核苷酸多态性研究较多。本研究的主要目的是探讨基因Interferon regulatory factor6(IRF6)的rs2235371和rs642961,8q24的rs987525和10q25的rs7078160与非综合征性唇腭裂的关系。在有些文献中,这四个单核苷酸多态性被认为是导致非综合征性唇腭裂的危险因素之一。然而,另一些文献则持相反观点。主要因为各研究样本含量有限的实际原因,研究结果不一致是客观存在的。增大样本含量是减少抽样误差的可靠方法,而Meta分析正是基于综合同质性较好的相关研究,增大样本含量的思想,使得合成后的结果能在更大程度上接近真实。为了弄清这四个单核苷酸多态性与非综合征性唇腭裂之间的真实关系,我们进行了一项尽可能纳入所有符合标准的研究的Meta分析。方法我们使用三个主要数据库,即MEDLINE(通过Pub Med检索平台),EMBASE(通过Ovid检索平台)和CENTRAL(通过Cochrane Library检索平台),来查找符合纳入标准的文献。两位作者独立判断文献能否纳入Meta分析,一致性通过Kappa值来评价。两位作者各自从纳入的文献中提取有关信息,不一致时通过协商或第三方裁定解决。Stata 12.0软件用于异质性检验、发表偏倚检验、敏感性分析及森林图、漏斗图制作。各研究中异质性检验水准以P〈0.05为差异有统计学意义。P〉0.05说明各研究间异质性较小,用固定效应模型合成统计量,反之则用随机效应模型合成数据。Newcastle-Ottawa量表用于评估纳入研究偏倚风险,其中4颗星以下提示该研究有高偏倚风险,4~6颗星为中等偏倚风险,7颗星以上为低偏倚风险。结果这四组Meta分析共纳入了25个符合纳入标准的原始研究。其中,探讨非综合征性唇腭裂与rs2235371之间关系的研究有10个,与rs642961有关的研究有7个,与rs987525有关的研究有10个,与rs7078160有关的研究有7个。使用Newcastle-Ottawa量表测量各研究偏倚风险大小,结果提示25项研究中低偏倚风险研究16个,中等偏倚风险研究9个。异质性检验结果P值分别为0.12、0.30、0.09、0.05,所以均用固定效应模型合成统计量。数据合成后显示,rs2235371(等位基因A vs等位基因G)能降低19%罹患非综合征性唇裂伴或不伴有腭裂风险(OR 0.81,95%CI 0.71~0.92),而rs642961(等位基因A vs等位基因G)、rs987525(等位基因A vs等位基因C)和rs7078160(等位基因A vs等位基因C)均分别增加103%、75%、32%罹患非综合征性唇裂伴或不伴有腭裂风险(OR2.03,95%CI 1.85~2.22;OR 1.75,95%CI 1.61~1.90;OR 1.32,95%CI 1.18~1.47)。无明显发表偏倚。敏感性分析结果稳定。结论总体来说,rs2235371是非综合征性唇腭裂的一个保护因素,而rs642961、rs987525和rs7078160促进非综合征性唇腭裂发生的三个高危因素。
[Abstract]:Objective in recent years, the single nucleotide polymorphism of cleft lip and palate has been studied.The main purpose of this study was to investigate the relationship between rs2235371 of Interferon regulatory factor6 gene and rs987525 of rs642961 and 10q25 and rs7078160 of non-syndromic cleft lip and palate.In some literature, these four single nucleotide polymorphisms are considered to be one of the risk factors for non-syndromic cleft lip and palate.Others, however, hold the opposite view.Mainly because of the limited sample size of each study, the results of the study are inconsistent and objective.Increasing the sample size is a reliable method to reduce the sampling error, and Meta analysis is based on the idea of increasing the sample size and synthesizing the homogeneity, which makes the synthesized results close to the reality to a greater extent.To understand the true relationship between these four SNP and non-syndromic cleft lip and palate we conducted a Meta analysis that included as many studies as possible.Methods We use three main databases, namely, MEDLINE (Pub Med search platform) and CENTRAL (Cochrane Library search platform) to find documents that meet the inclusion criteria.The authors independently judge whether the literature can be included in the Meta analysis, and the consistency is evaluated by the Kappa value.The two authors extracted relevant information from the included literature, and solved the problem by negotiation or third party ruling. Stata 12.0 software was used for heterogeneity test, publication bias test, sensitivity analysis, forest map and funnel map making.The heterogeneity test level of each study was significantly different from that of P < 0.05. P > 0.05 indicated that the heterogeneity of each study was small, and the statistics were synthesized by fixed effect model.On the contrary, the random effect model was used to synthesize data. Newcastle-Ottawa scale was used to evaluate the risk of inclusion bias.Results the four groups of Meta analysis included 25 original studies that met the inclusion criteria.Among them, there are 10 studies on the relationship between non-syndromic cleft lip and palate and rs2235371, 7 on rs642961, 10 on rs987525 and 7 on rs7078160.The Newcastle-Ottawa scale was used to measure the risk of bias in each study. The results showed that there were 16 middle and low bias risk studies and 9 moderate bias risk studies in 25 studies.The P values of heterogeneity test were 0.12 ~ 0.30 ~ 0.09 ~ 0.05, respectively, so the statistics were synthesized by fixed effect model.Allele A vs allele C) increased by 103% or 32% with or without the risk of cleft palate OR 1.853.22 OR 1.755 95 CI 1.61 1.90 OR 1.32% or 1.32% CI 1.181.47.There was no obvious bias towards publication.The sensitivity analysis results are stable.Conclusion generally speaking, rs2235371 is a protective factor for non-syndromic cleft lip and palate, while rs642961, rs987525 and rs7078160 promote the occurrence of non-syndromic cleft lip and palate.
【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R782.2

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