散发性胸主动脉瘤及夹层患者的TGFB2、TGFBR2及ACTA2基因突变的初步筛查研究

发布时间：2018-01-15 09:17

本文关键词：散发性胸主动脉瘤及夹层患者的TGFB2、TGFBR2及ACTA2基因突变的初步筛查研究　出处：《南昌大学》2015年硕士论文　论文类型：学位论文

【摘要】：研究背景与目的:胸主动脉瘤及夹层(TAAD)是一类临床上较常见的主动脉扩张性疾病。其致病因素多且复杂,急性期病死率高,约20%的病例有遗传倾向。近年来,越来越多的学者开始关注TAAD的发病与相关基因突变的关系,尤其是编码血管平滑肌细胞α-肌动蛋白的ACTA2及转化生长因子-β(TGF-β)信号通路上分别编码配合和受体的TGFB2、TGFBR2突变成为了研究的热点。本研究以散发性胸主动脉瘤(STAAD)患者的血液及病变组织标本为研究对象,旨在扩增ACTA2、TGFB2及TGFBR2的突变谱,并同时寻求血液及病变组织标本基因变异检出的差异。方法:经过严格筛选,30例STAAD患者和63例健康人群纳入了本研究项目,并自动分成病患组和对照组。病患组成员来自不同的家庭,入选个体间均无血缘关系。通过聚合酶链反应(PCR)和直接基因测序的方式来筛查目标基因的全部外显子,并应用Pymol软件绘制3D蛋白质模型展示基因变异,血液及病变组织标本基因变异检出的差异采用χ2检验(P0.05)。结果:本研究在病患组中检测出一个ACTA2错义突变(c.554 GA,p.R 185 Q),而未在对照组中筛出。同时我们还发现了一个TGFBR2基因多态性rs2228048(c.1167 CT,p.N 389 N),其中病患组的血液和病变组织样本分别检测出5个和13个,对照组检测出2个。这两种变异均已被报道。据统计学分析,病患组和对照组血液样本基因多态性的检出率及病患组血液和组织样本等位基因型频率均存在显著差异。结论:ACTA2错义突变(p.R 185 Q)和TGFBR2基因多态性rs2228048均可能是STAAD发病的遗传易感因素。在基因变异检测方面,病变组织样本的要优于血液样本。
[Abstract]:Background & objective: thoracic aortic aneurysm and dissection TAADA is a kind of common clinical aortic dilated disease with many and complex pathogenic factors and high acute mortality. About 20% cases have genetic tendency. In recent years, more and more scholars have begun to pay attention to the relationship between the pathogenesis of TAAD and related gene mutations. In particular, ACTA2 encoding 伪 -actin and transforming growth factor- 尾 (TGF- 尾) signal pathway encode the TGFB2 of coordination and receptor, respectively. TGFBR2 mutation has become a hot topic. The aim of this study was to amplify ACTA2 in blood and pathological tissues of patients with sporadic thoracic aortic aneurysm. The mutation profiles of TGFB2 and TGFBR2, and the difference of gene mutation in blood and pathological tissue samples were also sought. Methods: after strict screening. Thirty patients with STAAD and 63 healthy people were included in the study and were automatically divided into two groups: the patient group and the control group. The members of the patient group were from different families. All exons of the target gene were screened by polymerase chain reaction (PCR) and direct gene sequencing. Pymol software was used to draw 3D protein model to display gene mutation. Results: a ACTA2 missense mutation was detected in a patient group by 蠂 2 test (蠂 2 test). A polymorphic rs2228048(c.1167 CT of the TGFBR2 gene was also found in the control group. P. N389 NV, of which 5 and 13 blood and 13 pathological tissue samples were detected in the patient group and 2 in the control group. Both variants have been reported. There were significant differences in the detection rate of gene polymorphisms in blood samples and the allele frequencies of blood and tissue samples between patients and controls. Conclusion\% ACTA2 missense mutation p. R185 Q). Both rs2228048 polymorphism and TGFBR2 gene polymorphism may be the genetic susceptibility factors of STAAD. Pathological tissue samples are superior to blood samples.
【学位授予单位】：南昌大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R543.1

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