GPC1单核苷酸多态性与胆道闭锁易感性的关联研究

发布时间：2018-05-27 21:34

本文选题：胆道闭锁 + 全基因组关联性研究　；参考：《遵义医学院》2014年硕士论文

【摘要】：目的：胆道闭锁（Biliary atresia，BA）是新生儿阻塞性胆汁淤积的常见疾病，病因未明，其病理改变主要表现为反复炎症破坏及组织纤维化，致使肝内、肝外胆管进行性狭窄，最终导致闭锁。若出生后三个月内不及时治疗，患儿多在一岁左右夭折，，目前针对胆道闭锁患儿较为有效的治疗方法为葛西手术（Kasai手术），但是由于术后肝脏组织的持续破坏，绝大多数患儿需要进行肝移植才能达到远期存活的效果。本实验参照全基因组关联性研究(Genome-Wide Association Study, GWAS)近期的研究发现，2q37区域可能与胆道闭锁的发病具有相关性，参照国外学者运用斑马鱼对该区域行基因敲除实验的成果，依据Hapmap数据库，挑选2q37GPC1（rs3828336C＞T），以经深圳市儿童医院普外二科确诊为胆道闭锁患儿的外周静脉血及术中肝脏标本为实验材料，对GPC1（rs3828336C＞T）进行基因分型分析，评估该位点与中国人群胆道闭锁发病易感性是否具有相关性，并从胆道闭锁病因学基因层面提供相应线索。方法：采取以医院为标准的病例-对照研究方法，统计自2010年1月到2013年12月因梗阻性黄疸在深圳市儿童医院住院治疗，并经手术探查确诊为胆道闭锁的患儿136例作为实验组，其中男性患儿67例，女性患儿69例，并从来院治疗的除去肝胆疾病史的平诊患儿中按照与实验组性别相匹配的原则，随机抽取618例作为对照，其中男性儿童303例，女性儿童315例。分别从胆道闭锁患儿的外周静脉肝素抗凝血、术中肝脏标本及健康儿童外周静脉肝素抗凝血中提取DNA，应用Taqman探针基因分型技术分别对实验组和对照组2q37区域GPC1（rs3828336C＞T）进行基因分型，后期采用SPSS13.0软件分析数据，以此分析该位点单核苷酸多态性与中国人群胆道闭锁发病易感性的相关性。结果：1.所选取病例样本基本情况：本实验为病例-对照研究，所纳入研究的实验组胆道闭锁男性患儿67例，女性患儿69例，所占百分比各为49.3%和50.7%，对照组健康男性儿童303例，女性儿童315例，所占百分比各为49.0%和51.0%，经统计学分析得知，两组性别无统计学差异（P=0.96）。2.针对GPC1（rs3828336C＞T）分析：本实验通过分析得知，GPC1（rs3828336C＞T）与中国人群胆道闭锁患儿发病易感性无统计学差异，与疾病易感性无明显关联。结论：通过本次研究显示，GPC1（rs3828336C＞T）与中国人群胆道闭锁发病易感性未见明显关联。
[Abstract]:Objective: biliary atresia (Biliary atresia BAA) is a common disease of neonatal obstructive cholestasis with unknown etiology. The pathological changes of Biliary atresia are repeated inflammation destruction and tissue fibrosis, leading to progressive stricture of intrahepatic and extrahepatic bile ducts, and finally to atresia. If there is no timely treatment within three months after birth, most of the children die at the age of one year or so. At present, the more effective treatment for children with biliary atresia is Kasai's operation, but due to the continuous destruction of liver tissue after operation, Most children need liver transplantation to achieve long-term survival. According to the genome-Wide Association Study, GWAS) recent study, we found that the 2q37 region may be related to the pathogenesis of biliary atresia. According to the results of the experiments of zebrafish gene knockout in this region, we used Hapmap database. The blood samples of peripheral vein and liver of children with biliary atresia diagnosed by the second Department of Common Foreign Medicine of Shenzhen Children's Hospital were selected as experimental materials. The genotyping of GPC1(rs3828336C > T was analyzed. To evaluate the correlation between this locus and the susceptibility to biliary atresia in Chinese population, and to provide clues from the gene level of biliary atresia etiology. Methods: from January 2010 to December 2013, 136 children with biliary atresia were admitted to Shenzhen Children's Hospital from January 2010 to December 2013. Among them, 67 cases were male, 69 cases were female, and 618 cases were randomly selected as control group according to the principle of matching sex with experimental group, among them 303 cases were male children. 315 female children. DNA was extracted from peripheral vein heparin anticoagulant of children with biliary atresia, liver samples during operation and peripheral venous heparin anticoagulant blood from healthy children. The 2q37 region GPC1(rs3828336C > T of the experimental group and the control group were genotyped by Taqman probe genotyping technique, respectively. SPSS13.0 software was used to analyze the relationship between the single nucleotide polymorphism and the susceptibility to biliary atresia in Chinese population. The result is 1: 1. The basic information of selected cases: this study was a case-control study. There were 67 male and 69 female children with biliary atresia in the experimental group. The percentages were 49.3% and 50.7%, respectively. 303 healthy male children in the control group were included in the study. The percentages of 315 female children were 49.0% and 51.0%, respectively. The statistical analysis showed that there was no statistical difference between the two groups. According to the analysis of GPC1(rs3828336C > T: this experiment shows that there is no significant difference between GPC1, rs3828336C > T) and the susceptibility of children with biliary atresia in China, but there is no significant correlation between GPC1rs38336C and disease susceptibility. Conclusion: there is no significant correlation between GPC1 rs3828336C > T and the susceptibility to biliary atresia in Chinese population.
【学位授予单位】：遵义医学院
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R726.5

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