本文選題：IRF6 + 8q24��； 參考：《安徽醫(yī)科大學(xué)》2015年碩士論文

【摘要】：目的近年來,有關(guān)唇腭裂的單核苷酸多態(tài)性研究較多。本研究的主要目的是探討基因Interferon regulatory factor6(IRF6)的rs2235371和rs642961,8q24的rs987525和10q25的rs7078160與非綜合征性唇腭裂的關(guān)系。在有些文獻(xiàn)中,這四個單核苷酸多態(tài)性被認(rèn)為是導(dǎo)致非綜合征性唇腭裂的危險因素之一。然而,另一些文獻(xiàn)則持相反觀點。主要因為各研究樣本含量有限的實際原因,研究結(jié)果不一致是客觀存在的。增大樣本含量是減少抽樣誤差的可靠方法,而Meta分析正是基于綜合同質(zhì)性較好的相關(guān)研究,增大樣本含量的思想,使得合成后的結(jié)果能在更大程度上接近真實。為了弄清這四個單核苷酸多態(tài)性與非綜合征性唇腭裂之間的真實關(guān)系,我們進(jìn)行了一項盡可能納入所有符合標(biāo)準(zhǔn)的研究的Meta分析。方法我們使用三個主要數(shù)據(jù)庫,即MEDLINE(通過Pub Med檢索平臺),EMBASE(通過Ovid檢索平臺)和CENTRAL(通過Cochrane Library檢索平臺),來查找符合納入標(biāo)準(zhǔn)的文獻(xiàn)。兩位作者獨立判斷文獻(xiàn)能否納入Meta分析,一致性通過Kappa值來評價。兩位作者各自從納入的文獻(xiàn)中提取有關(guān)信息,不一致時通過協(xié)商或第三方裁定解決。Stata 12.0軟件用于異質(zhì)性檢驗、發(fā)表偏倚檢驗、敏感性分析及森林圖、漏斗圖制作。各研究中異質(zhì)性檢驗水準(zhǔn)以P〈0.05為差異有統(tǒng)計學(xué)意義。P〉0.05說明各研究間異質(zhì)性較小,用固定效應(yīng)模型合成統(tǒng)計量,反之則用隨機(jī)效應(yīng)模型合成數(shù)據(jù)。Newcastle-Ottawa量表用于評估納入研究偏倚風(fēng)險,其中4顆星以下提示該研究有高偏倚風(fēng)險,4~6顆星為中等偏倚風(fēng)險,7顆星以上為低偏倚風(fēng)險。結(jié)果這四組Meta分析共納入了25個符合納入標(biāo)準(zhǔn)的原始研究。其中,探討非綜合征性唇腭裂與rs2235371之間關(guān)系的研究有10個,與rs642961有關(guān)的研究有7個,與rs987525有關(guān)的研究有10個,與rs7078160有關(guān)的研究有7個。使用Newcastle-Ottawa量表測量各研究偏倚風(fēng)險大小,結(jié)果提示25項研究中低偏倚風(fēng)險研究16個,中等偏倚風(fēng)險研究9個。異質(zhì)性檢驗結(jié)果P值分別為0.12、0.30、0.09、0.05,所以均用固定效應(yīng)模型合成統(tǒng)計量。數(shù)據(jù)合成后顯示,rs2235371(等位基因A vs等位基因G)能降低19%罹患非綜合征性唇裂伴或不伴有腭裂風(fēng)險(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)均分別增加103%、75%、32%罹患非綜合征性唇裂伴或不伴有腭裂風(fēng)險(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)。無明顯發(fā)表偏倚。敏感性分析結(jié)果穩(wěn)定。結(jié)論總體來說,rs2235371是非綜合征性唇腭裂的一個保護(hù)因素,而rs642961、rs987525和rs7078160促進(jìn)非綜合征性唇腭裂發(fā)生的三個高危因素。
[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.
【學(xué)位授予單位】：安徽醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R782.2

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