组织血型抗原基因多态性与溃疡性结肠炎的相关性研究
发布时间：2018-11-27 11:29
【摘要】：目的： 炎症性肠病(inflammatory bowel diseases, IBD)是一组病因不明的慢性肠道非特异性炎症性疾病,主要包括溃疡性结肠炎(ulcerative colitis, UC)和克罗恩病(Crohn's disease, CD)。目前研究证实肠道菌群失调在IBD的发病机制中起关键作用。组织血型抗原是某些肠道菌群的粘附受体,这些抗原的表达主要是由岩藻糖基转移酶(FUT)2和FUT3基因编码产生的岩藻糖基转移酶调控的。研究表明FUT2基因多态性不仅与肠道菌群的构成相关,还与1型糖尿病、原发性硬化性胆管炎等自身免疫性疾病的易感性有关。至今针对FUT2与IBD相关性的研究证实FUT2基因是CD的易感基因,但与UC的关系尚不明确。此外,目前罕见FUT3基因多态性与UC的易感性研究。鉴于FUT2和FUT3基因在调控组织血型抗原的表达过程中具有协同作用,本研究拟在中国浙江汉族人群中同时探讨FUT2和FUT3基因多态性及单倍型与UC的关系,旨在为阐明UC的遗传学发病机制提供依据。 方法： 于2008年5月-2013年5月间,从包括温州医科大学附属第二医院、温州医科大学附属第一医院及温州市中心医院等在内的温州市各大中型医院的消化内科门诊和住院部,收集确诊的UC患者233例,UC的诊断标准和疾病评估标准根据中华医学会消化病学分会2012年制定的“炎症性肠病诊断与治疗的共识意见”。同期在温州医科大学附属第二医院体检中心收集292例性别、年龄匹配的健康对照组。从每个受试对象抽取约5ml外周静脉血至EDTA抗凝管中。提取全基因组DNA后经多重PCR扩增目的基因,再采用SNaPshot法检测FUT2(C357T、A385T、G428A)和FUT3(T59G、G508A、T1067A)基因多态性。用χ2检验分析上述各位点的基因型分布是否符合Hardy-Weinberg平衡定律,并分析UC组和正常对照组之间,各位点的等位基因和基因型的频率差别。采用Haploview4.2软件进行连锁平衡和单倍型分析。多因子降维法分析基因-基因交互作用(FUT2和FUT3基因)和基因-环境(吸烟)交互作用。 结果： 经重复检测和直接测序法验证,SNaPshot法基因分型的准确率为100%。各位点的基因型分布均符合Hardy-Weinberg平衡定律。在UC组和对照组之间,FUT2(C357T、A385T、G428A)和FUT3(T59G, G508A、T1067A)六个位点的等位基因与基因型频率分布均无统计学差异(均P0.05)。经非条件Logistic回归分析发现在广泛结肠炎患者中,FUT3(T59G)的突变等位基因(G)和基因型(TG+GG)的频率低于直肠型和左半结肠型UC患者[17.5%(35/200)比25.9%(69/266)，，P=0.022, OR=0.530,95%CI:0.308-0.914和31.0%(31/100)比45.9%(61/133), P=0.030, OR=0.606,95%CI:0.384-0.956]。进一步连锁不平衡分析发现,FUT2和FUT3两基因之间不存在连锁不平衡,但发现FUT2基因(C357T)和(A385T)两个位点存在连锁不平衡(D'=1.00,r2=0.102)；FUT3基因(T59G)和(G508A)两个位点也存在连锁不平衡(D'=0.95,r2=0.508)。采用Haploview4.2软件构建单倍型后,结果表明各单倍型在UC组和对照组之间的分布无统计学差异(均P0.05)。多因子降维法分析这表明FUT2和FUT3基因,以及基因-环境(吸烟)之间不存在交互作用。 结论： FUT2基因多态性及单倍型与UC的易感性无关；FUT3(T59G)基因突变可能影响UC患者的病变部位。
[Abstract]:Purpose: Inflammatory bowel disease (IBD) is a group of non-specific inflammatory diseases of chronic intestinal tract, including ulcerative colitis (UC) and Crohn's disease (CD).). At present, it is proved that the intestinal flora imbalance plays a key role in the pathogenesis of IBD The expression of these antigens is mainly regulated by the glycosyltransferase (FUT) 2 and the encoding of the FUT3 gene, and the expression of these antigens is mainly regulated by the encoding of the glycosyltransferase (FUT) 2 and the FUT3 gene. The research shows that the polymorphism of the FUT2 gene is not only related to the composition of the intestinal flora, but also the susceptibility of autoimmune diseases such as type 1 diabetes, primary sclerosing cholangitis and the like. The relationship between FU2 and IBD has confirmed that the FU2 gene is an easy-to-sense gene of the CD, but the relationship with the UC is unknown. in addition, it is rare that that polymorphism of the Fut3 gene and the susceptibility to UC are rare. In view of the synergistic effect of FU2 and FUT3 gene in regulating the expression of blood group antigen of tissue, this study is to study the relationship between FU2 and Fut3 gene polymorphism and single-fold and UC in the Han population of Zhejiang, China, aiming at providing the basis for elucidating the genetic pathogenesis of UC. It was reported. Methods: From May 2008 to May, 2013, the patients with UC were collected from the Department of Internal Medicine and the Hospitalization Department, including the Second Affiliated Hospital of Wenzhou Medical University, the First Affiliated Hospital of Wenzhou Medical University and the Central Hospital of Wenzhou. In 233 cases, the criteria for the diagnosis of UC and the criteria for the assessment of the disease are based on the criteria for the diagnosis of digestive diseases of the Chinese Medical Association, which will be formulated in 2012./ trunk>. In the same period, 292 cases of sex and age were collected in the second hospital in Wenzhou Medical University. Healthy control group. Approximately 5ml of peripheral venous blood was extracted from each subject to the EDT A anti-coagulation tube. After the whole genome DNA is extracted, the target gene is amplified by multiple PCR, and the FUT2 (C357T, A385T, G428A) and FUT3 (T59G, G508A, T1067A) are detected by the SNaPshot method. The genotype distribution of the above-mentioned points was analyzed by means of a two-step method to determine whether the Hardy-Weinberg equilibrium law was in line with the Hardy-Weinberg equilibrium law, and the alleles and genotypes of each point were analyzed between the UC group and the normal control group. the frequency difference of the system is different, and the linkage balance is carried out by using the Hapaloview4. 2 software. Single-fold analysis. Analysis of gene-gene interaction (FU2 and FUT3 genes) and gene-environment (smoking) Interaction Action. Results: The gene typing of the SNaPshot method was verified by repeated detection and direct sequencing. The accuracy rate is 100%. The genotype distribution of all points is in accordance with Hardy-Wei. The law of nberg equilibrium. There was no statistical difference between the alleles of FU2 (C357T, A385T, G428A) and FUT3 (T59G, G508A, T1067A) and the distribution of genotype frequencies between the UC and the control group. The frequency of mutant allele (G) and genotype (TG + GG) of FUT3 (T59G) in patients with extensive colitis was found to be lower than that of the patients with colorectal and left-and semi-colon UC[170.5% (35/ 200), 25.9% (69/ 266), P = 0.022, OR = 0.530, 95% CI: 0.308-0.914 and 31.0% (31/ 100) than 40.9% (61/ 133), P = 0.030, OR = 0.606, 95% CI: 0.3 The further linkage disequilibrium analysis found that there was no linkage disequilibrium between the two genes of FU2 and Fut3, but the linkage disequilibrium (D '= 1.00, r2 = 0.102) was found between the two sites of the FUT2 gene (C357T) and (A385T), and the linkage disequilibrium (D' = 0.95, r2 = 0. 508) The results showed that the distribution of the single-fold type in the UC group and the control group was not statistically significant after the single-fold type was constructed using the Hapaloview4. 2 software. Isomorphism (all P0.05). The multi-factor descending method analysis showed that the FU2 and FUT3 genes, as well as the gene-environment (smoking) No, no, no. Conclusion: The polymorphism of FU2 gene and the susceptibility of single-fold to UC are not related to the susceptibility to UC, and the gene mutation of FUT3 (T59G)
【学位授予单位】：武汉大学
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R574.62
本文编号：2360582
[Abstract]:Purpose: Inflammatory bowel disease (IBD) is a group of non-specific inflammatory diseases of chronic intestinal tract, including ulcerative colitis (UC) and Crohn's disease (CD).). At present, it is proved that the intestinal flora imbalance plays a key role in the pathogenesis of IBD The expression of these antigens is mainly regulated by the glycosyltransferase (FUT) 2 and the encoding of the FUT3 gene, and the expression of these antigens is mainly regulated by the encoding of the glycosyltransferase (FUT) 2 and the FUT3 gene. The research shows that the polymorphism of the FUT2 gene is not only related to the composition of the intestinal flora, but also the susceptibility of autoimmune diseases such as type 1 diabetes, primary sclerosing cholangitis and the like. The relationship between FU2 and IBD has confirmed that the FU2 gene is an easy-to-sense gene of the CD, but the relationship with the UC is unknown. in addition, it is rare that that polymorphism of the Fut3 gene and the susceptibility to UC are rare. In view of the synergistic effect of FU2 and FUT3 gene in regulating the expression of blood group antigen of tissue, this study is to study the relationship between FU2 and Fut3 gene polymorphism and single-fold and UC in the Han population of Zhejiang, China, aiming at providing the basis for elucidating the genetic pathogenesis of UC. It was reported. Methods: From May 2008 to May, 2013, the patients with UC were collected from the Department of Internal Medicine and the Hospitalization Department, including the Second Affiliated Hospital of Wenzhou Medical University, the First Affiliated Hospital of Wenzhou Medical University and the Central Hospital of Wenzhou. In 233 cases, the criteria for the diagnosis of UC and the criteria for the assessment of the disease are based on the criteria for the diagnosis of digestive diseases of the Chinese Medical Association, which will be formulated in 2012./ trunk>. In the same period, 292 cases of sex and age were collected in the second hospital in Wenzhou Medical University. Healthy control group. Approximately 5ml of peripheral venous blood was extracted from each subject to the EDT A anti-coagulation tube. After the whole genome DNA is extracted, the target gene is amplified by multiple PCR, and the FUT2 (C357T, A385T, G428A) and FUT3 (T59G, G508A, T1067A) are detected by the SNaPshot method. The genotype distribution of the above-mentioned points was analyzed by means of a two-step method to determine whether the Hardy-Weinberg equilibrium law was in line with the Hardy-Weinberg equilibrium law, and the alleles and genotypes of each point were analyzed between the UC group and the normal control group. the frequency difference of the system is different, and the linkage balance is carried out by using the Hapaloview4. 2 software. Single-fold analysis. Analysis of gene-gene interaction (FU2 and FUT3 genes) and gene-environment (smoking) Interaction Action. Results: The gene typing of the SNaPshot method was verified by repeated detection and direct sequencing. The accuracy rate is 100%. The genotype distribution of all points is in accordance with Hardy-Wei. The law of nberg equilibrium. There was no statistical difference between the alleles of FU2 (C357T, A385T, G428A) and FUT3 (T59G, G508A, T1067A) and the distribution of genotype frequencies between the UC and the control group. The frequency of mutant allele (G) and genotype (TG + GG) of FUT3 (T59G) in patients with extensive colitis was found to be lower than that of the patients with colorectal and left-and semi-colon UC[170.5% (35/ 200), 25.9% (69/ 266), P = 0.022, OR = 0.530, 95% CI: 0.308-0.914 and 31.0% (31/ 100) than 40.9% (61/ 133), P = 0.030, OR = 0.606, 95% CI: 0.3 The further linkage disequilibrium analysis found that there was no linkage disequilibrium between the two genes of FU2 and Fut3, but the linkage disequilibrium (D '= 1.00, r2 = 0.102) was found between the two sites of the FUT2 gene (C357T) and (A385T), and the linkage disequilibrium (D' = 0.95, r2 = 0. 508) The results showed that the distribution of the single-fold type in the UC group and the control group was not statistically significant after the single-fold type was constructed using the Hapaloview4. 2 software. Isomorphism (all P0.05). The multi-factor descending method analysis showed that the FU2 and FUT3 genes, as well as the gene-environment (smoking) No, no, no. Conclusion: The polymorphism of FU2 gene and the susceptibility of single-fold to UC are not related to the susceptibility to UC, and the gene mutation of FUT3 (T59G)
【学位授予单位】：武汉大学
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R574.62
【相似文献】
相关期刊论文 前10条
1 本刊编辑部;;吉林和山西两省人群Rh血型抗原分布[J];中国输血杂志;1992年02期
2 胡利亚,张惠兰,兰炯采;2例骨髓增生异常综合征血型抗原减弱的连续观察[J];上海医学检验杂志;1993年04期
3 Maria Rios ,Celso Bianco ,李芳;血型抗原在传染病中的作用[J];国外医学.输血及血液学分册;2001年05期
4 李宗民,刘秀梅,李亚冬,王振玲;血型抗原减弱1例报告[J];中国热带医学;2004年01期
5 张春来,陈晓建,于咏梅,谷彦霞,陈召江,杨振中;应用柱凝集技术进行Rh血型抗原分型的研究[J];临沂医学专科学校学报;2004年02期
6 李大鹏,武琴,李荷,徐学芳,任红,冯永军;军队427名汉族官兵Rh血型抗原分布调查分析[J];临床军医杂志;2005年04期
7 侯萍;宋志国;王玉琴;;血型抗原功能及与疾病的相关性探讨[J];中国误诊学杂志;2010年30期
8 杨连甲;在造釉细胞瘤、牙源性角化囊肿和非角化囊肿时A和B血型抗原[J];国外医学参考资料.口腔医学分册;1977年01期
9 褚殿儒;;血型抗原改变一例报告[J];河北新医药;1979年03期
10 司履生,袁定东,郭尚温;食管鳞状细胞癌中的A、B血型抗原[J];西安交通大学学报(医学版);1981年01期
相关会议论文 前8条
1 邱艳;查垎;杨海平;李立立;张志欣;章扬培;;Rh血型抗原化学修饰材料的选择[A];中国输血协会第四届输血大会论文集[C];2006年
2 聂海祺;;骨髓增生异常综合征致血型抗原减弱1例[A];中国输血协会第三届输血大会论文专辑[C];2004年
3 王保捷;丁梅;肖仰哲;李春梅;张核子;卢岩;王琪;;唾液血型抗原分泌时限变化及温度对抗原活性的影响[A];第二次全国法医物证学学术交流会论文集[C];1998年
4 赵阳兵;赵雄飞;路淑珍;;培养人表皮细胞及其异体移植后ABH血型抗原变化的观察[A];全国第三届烧伤外科学术交流会议论文摘要[C];1991年
5 李国良;孙瑜;肖莉;唐绮;后平钦;张荣艳;;异基因造血干细胞移植后STR和血型抗原变化的观察[A];中国输血协会第三届输血大会论文专辑[C];2004年
6 卓孝福;陈静静;郭永建;;人红细胞RhD血型抗原的甲氧基聚乙二醇修饰研究[A];中国输血协会第五届输血大会论文专集（摘要篇）[C];2010年
7 张然;郑敏;赵要风;李宁;;转基因小鼠乳汁中岩藻糖化Lewis b血型抗原结合幽门螺杆菌的初步研究[A];中国生物工程学会2006年学术年会暨全国生物反应器学术研讨会论文摘要集[C];2006年
8 赵凤萍;朱海田;刘郁;高秀俊;陈平香;;RhD阴性献血者Rh血型抗原表型鉴定在临床输血中的重要作用[A];中国输血协会第四届输血大会论文集[C];2006年
相关博士学位论文 前3条
1 刘武;诺如病毒与组织血型抗原结合机制的研究[D];中国科学技术大学;2015年
2 徐昌隆;组织血型抗原基因多态性与溃疡性结肠炎的相关性研究[D];武汉大学;2014年
3 马丽萍;贝类中诺如病毒的风险评估及与组织血型抗原相关性[D];上海海洋大学;2013年
相关硕士学位论文 前2条
1 田庆;外切糖苷酶清除人体器官血型抗原的实验研究[D];天津医科大学;2014年
2 徐华;甲氧基聚乙二醇修饰人红细胞稀有血型抗原的研究[D];中国人民解放军军事医学科学院;2004年
本文编号：2360582
本文链接：https://www.wllwen.com/yixuelunwen/xiaohjib/2360582.html
最近更新
教材专著
