【摘要】：目的：先天性巨結(jié)腸(Hirschsprung's Disease, HSCR)又稱腸管無神經(jīng)節(jié)細(xì)胞癥,是小兒常見的先天性消化道畸形,發(fā)病率居先天性消化道畸形第二位,以不同病變范圍內(nèi)腸段肌間神經(jīng)叢和粘膜下神經(jīng)叢神經(jīng)節(jié)細(xì)胞的缺失為主要病理學(xué)特征。目前研究證明它是一種的多基因型疾病,是多個(gè)基因位點(diǎn)相互作用的結(jié)果,其中最主要的基因是RET原癌基因(RET proto-oncogen)。RET基因具有多態(tài)性和單倍型,可能作為基因修飾因子,而且可能神經(jīng)嵴胚細(xì)胞發(fā)育過程中發(fā)生紊亂的危險(xiǎn)性增加與之相關(guān)。本研究通過深圳地區(qū)先天性巨結(jié)腸患兒RET基因上intronlCT (rs2435357)單核苷酸多態(tài)性的研究及基因多態(tài)表達(dá)情況,明確其與HSCR的關(guān)聯(lián)性,揭示intronlCT(rs2435357)多態(tài)性在深圳地區(qū)人群散發(fā)性HSCR發(fā)病中所起的重要作用,探討其與HSCR發(fā)病風(fēng)險(xiǎn)的關(guān)系,并為HSCR的發(fā)病機(jī)制提供線索。 方法：收集2008年5月至2011年8月在深圳市兒童醫(yī)院外科診治的HSCR患兒的靜脈全血標(biāo)本115例,均為散發(fā)性,其中男90例,女25例,患有TCA(全結(jié)腸型先天性巨結(jié)腸),L-HSCR(長段型先天性巨結(jié)腸)和S-HSCR(短段型先天性巨結(jié)腸)的病人分別為4人,6人和105人,年齡17天-81天,無先天性巨結(jié)腸家族性遺傳病史。所有患者均經(jīng)術(shù)后病理組織學(xué)確認(rèn)為HSCR。收集139名性別和年齡與之匹配的來源于深圳市兒童醫(yī)院體檢的正常兒童靜脈全血標(biāo)本作為對照組。抽取研究樣本靜脈全血3ml使用QIAamp-Blood Kit (Qiagen, Hilden,Germany)試劑盒進(jìn)行提取血樣本基因組DNA,聚合酶鏈反應(yīng)(polymerase chain reaction, PCR)擴(kuò)增RET基因intronl CT(rs2435357),然后應(yīng)用直接測序方法分析intronl CT(rs2435357)的基因多態(tài)性改變,對基因多態(tài)性位點(diǎn)等位基因頻率在兩組中的差異進(jìn)行比較,比較不同基因型與先天性巨結(jié)腸風(fēng)險(xiǎn)的相關(guān)性�；貧w模型中使用OR值和95%置信區(qū)間(CI)作為基因型危險(xiǎn)性的評價(jià)指標(biāo)。 結(jié)果：RET基因intronlCT(rs2435357)基因頻率在病例和正常對照人群的分布具有顯著差異(P0.001),攜帶RET基因intronlTT基因型者罹患先天性巨結(jié)腸的風(fēng)險(xiǎn)是攜帶RET intron1CC基因型者的19.22倍(95%CI,7.54-48.99)。RET基因intronl TT(OR=19.22,95%CI=7.54-48.99)基因型能明顯增加HSCR發(fā)病的風(fēng)險(xiǎn)。 結(jié)論：RET基因intronlCT(rs2435357)單核苷酸多態(tài)可能是深圳地區(qū)發(fā)生先天性巨結(jié)腸的遺傳易感因素
[Abstract]:Objective: congenital Hirschsprung's disease (Hirschsprung's Disease, HSCR) is a common congenital alimentary tract malformation in children. The main pathological features were the absence of ganglion cells in the myenteric plexus and submucosal plexus in different lesions. At present, it has been proved to be a multi-genotypic disease, which is the result of the interaction of multiple gene loci. The most important gene is the proto-oncogene of RET (RET proto-oncogen). RET gene is polymorphic and haplotype). It may be a genetically modified factor and may be associated with an increased risk of disorder in the development of neural crest embryonic cells. In this study, we studied the single nucleotide polymorphisms of intronlCT (rs2435357) on RET gene and gene polymorphism expression in children with Hirschsprung's disease in Shenzhen area to determine its association with HSCR. To reveal the important role of intronlCT (rs2435357) polymorphism in sporadic HSCR in Shenzhen area, to explore its relationship with the risk of HSCR, and to provide clues for the pathogenesis of HSCR. Methods: from May 2008 to August 2011, the venous blood samples of 115 patients with HSCR were collected, including 90 males and 25 females, with TCA (total colonic Hirschsprung's disease). Patients with L-HSCR (long segment Hirschsprung's disease) and S-HSCR (short segment Hirschsprung's disease) were 4, 6 and 105, respectively. Their age was 17 days to 81 days. There was no history of familial hereditary disease of Hirschsprung's disease. All patients were confirmed as HSCR. by postoperative histopathology. A total blood sample of 139 healthy children with matched sex and age was collected from Shenzhen Children's Hospital as control group. The genomic DNA, polymerase chain reaction (polymerase chain reaction, PCR) amplification of RET gene intronl CT (rs2435357 was carried out by using QIAamp-Blood Kit (Qiagen, Hilden,Germany kit to extract the whole blood 3ml from the study samples. Then the genetic polymorphisms of intronl CT (rs2435357) were analyzed by direct sequencing. The allelic frequencies of polymorphic loci were compared between the two groups, and the correlation between different genotypes and the risk of Hirschsprung's disease (Hirschsprung's disease) was compared. OR value and 95% confidence interval (CI) were used to evaluate genotype risk in regression model. Results: the frequency of intronlCT (rs2435357) gene of RET gene was significantly different between the case and the control group (P0. 001). People with intronlTT genotype of RET gene were 19.22 times more likely to develop congenital megacolon than those with RET intron1CC genotype. The 7.54-48.99). RET gene intronl TT (OR=19.22,95%CI=7.54-48.99) genotype significantly increased the risk of HSCR. Conclusion: the single nucleotide polymorphism of RET intronlCT (rs2435357) may be the genetic susceptibility factor of Hirschsprung's disease in Shenzhen area.
【學(xué)位授予單位】：遵義醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2012
【分類號】：R726.5

【共引文獻(xiàn)】

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