克罗恩病CNTNAP3基因拷贝数变异及其意义  

CNTNAP3 Copy Number Variation and its Significance in Crohn's Disease

作　　者：黄美兰[1] 乔宇琪[2] 沈骏[2] 蔡晨雯[2] 徐锡涛[2] 陈胜良[1] 冉志华[2] 

机构地区：[1]上海交通大学医学院附属仁济医院南院消化内科,201112 [2]上海交通大学医学院附属仁济医院消化内科上海市消化疾病研究所上海市炎症性肠病研究中心

出　　处：《胃肠病学》2017年第6期325-330,共6页Chinese Journal of Gastroenterology

基　　金：国家自然科学基金(81500422)

摘　　要：背景:DNA拷贝数变异是人类疾病的重要致病因素,可能参与了炎症性肠病(IBD)的发病机制和病理过程。目的:探讨CNTNAP3基因在克罗恩病(CD)中的拷贝数变异情况及其意义。方法:纳入2009年7月—2010年12月上海交通大学医学院附属仁济医院收治的活动期CD患者101例,同期80例健康体检者作为正常对照。采集CD患者外周血或肠黏膜标本,以比较基因组杂交芯片(a CGH,n=8)和荧光定量PCR(n=93)筛选、验证CNTNAP3基因拷贝数变异,ELISA法(n=55)检测CNTNAP3编码蛋白表达。结果:a CGH检测显示初发CD患者染色体9p13区域(含CNTNAP3基因)存在大片段拷贝数扩增;荧光定量PCR验证并确认CD组外周血CNTNAP3基因拷贝数显著高于正常对照组,非激素治疗组差异更为明显(208 616.4±126 984.7和233 453.3±113 520.8对161 750.2±53 940.3,P<0.05和P<0.01)。在各项CD临床参数中,仅吸烟史与CNTNAP3基因拷贝数扩增显著相关(P<0.05),但拷贝数明显扩增者的血浆CNTNAP3水平与正常对照组无明显差异(P>0.05),与简化CD内镜评分无相关性(P>0.05)。结论:CNTNAP3基因拷贝数扩增可能参与了中国CD人群的发病,激素治疗和吸烟可能是影响该基因拷贝数变异的因素;血浆CNTNAP3水平不能用于区分CD患者与健康人。本研究结论有待进一步验证。Background： DNA copy number variation is an important pathogenic factor of human diseases and might be involved in the pathogenesis and pathological process of inflammatory bowel disease（ IBD）. Aims： To investigate the copy number variation of CNTNAP3 gene and its significance in Crohn＇s disease（ CD）. Methods： A total of 101 active CD patients admitted from Jul. 2009 to Dec. 2010 at Renji Hospital,School of Medicine,Shanghai Jiao Tong University were enrolled.Eighty healthy subjects were served as controls. Peripheral blood or intestinal mucosa samples of CD patients were collected,and the copy number variation of CNTNAP3 gene was screened and validated by array-based comparative genomic hybridization（ aC GH,n = 8） and real-time PCR（ n = 93）; expression of CNTNAP3 encoding protein was determined by ELISA（ n = 55）. Results： A large fragment copy number amplification was revealed by aC GH at chromosome 9p13 region（ including CNTNAP3 gene） in untreated CD patients. Real-time PCR confirmed that the copy number of CNTNAP3 gene was amplified in peripheral blood of CD patients,especially steroid-naive patients as compared with the normal controls（ 208 616. 4 ± 126 984. 7 and 233 453. 3 ± 113 520. 8 vs. 161 750. 2 ± 53 940. 3,P〈0. 05 and P〈0. 01）. In the clinical parameters analyzed in this study,only smoking was significantly correlated with CNTNAP3 copy number amplification（ P〈0. 05）. However,there was no significant difference in plasma CNTNAP3 level between CD patients with amplified copy number and normal controls（ P〉0. 05）. Furthermore,the plasma CNTNAP3 level in CDpatients with amplified copy number was not correlated with the simplified endoscopic score for CD（ P〈0. 05）.Conclusions： Copy number amplification of CNTNAP3 gene might be involved in the pathogenesis of CD in Chinese population. Glucocorticoid treatment and smoking might affect the copy number variation of CNTNAP3 gene. Plasma CNTNAP3 level cannot discriminate CD patients from healthy sub

关 键 词：炎症性肠病 CROHN病 DNA拷贝数变异 CNTNAP3基因 比较基因组学 

分 类 号：R574.62[医药卫生—消化系统]