整联蛋白α4和细胞间黏附分子1基因多态性与克罗恩病发病风险及其临床病理特征的相关性

doi:10.3760/cma.j.cn511374-20221103-00755

科研成果详情

题名	整联蛋白α4和细胞间黏附分子1基因多态性与克罗恩病发病风险及其临床病理特征的相关性
其他题名	Association of ITGA4 and ICAM-1 gene polymorphisms with the risk and clinicopathological characteristics of Crohn′s disease
作者	张顶力; 吴昊; 邵晓晓; 肖慧盈; 蒋益
发表日期	2024-02-10
发表期刊	中华医学遗传学杂志影响因子和分区
语种	中文
原始文献类型	Periodical
关键词	克罗恩病整联蛋白α4 细胞间黏附分子1 基因多态性
其他关键词	Crohn′s disease ; Integral protein α4 ; Intercellular adhesion molecule 1 ; Genetic polymorphism
摘要	目的:探讨整联蛋白α4( ITGA4)和细胞间黏附分子1( ICAM-1)基因的多态性与克罗恩病(CD)的发病风险及临床病理特征之间的相关性。方法:收集2010年1月至2021年1月于温州医科大学附属第二医院消化内科确诊的215例CD患者及性别、年龄相匹配的529名正常对照者。应用基质辅助激光解吸电离-时间飞行质谱技术检测 ITGA4(rs6740847、rs7562325)和 ICAM-1(rs5498)的基因型。采用Harvey-Bradshaw指数(HBI)评估CD的疾病活动度，并依据蒙特利尔CD表型分类标准将CD患者分层。采用非条件Logistic回归分析 ITGA4(rs6740847、rs7562325)和 ICAM-1(rs5498)基因多态性在CD组和正常对照组之间的分布差异及其对CD临床病理特征的影响。结果:CD组 ITGA4(rs7562325)的变异等位基因(T)和变异基因型(CT＋TT)的频率均高于正常对照组(40.70% vs. 31.57%， P＝0.001；62.79% vs. 54.36%， P＝0.042)。中重度活动期CD患者 ITGA4(rs6740847)的变异等位基因(G)和变异基因型(AG＋GG)的频率均低于轻度活动期CD患者(31.18% vs. 51.72%， P＝0.002；55.91% vs. 75.86%， P＝0.042)；中重度活动期CD患者 ICAM-1(rs5498)的变异等位基因(G)和变异基因型(AG＋GG)的频率均高于轻度活动期CD患者(31.45% vs. 17.24%， P＝0.027；54.30% vs. 31.04%， P＝0.020)。与(回肠末端型＋回结肠型)CD患者比较，结肠型CD患者 ITGA4(rs6740847)的变异等位基因(G)和变异基因型(AG＋GG)的频率显著偏高(55.26% vs. 29.38%， P<0.000 1；84.21% vs. 53.11%， P<0.000 1)， ICAM-1(rs5498)的变异等位基因(G)和变异基因型(AG＋GG)的频率亦显著偏高(42.11% vs. 26.84%， P＝0.008；73.69% vs. 46.33%， P＝0.002)。(狭窄型＋穿透型)CD患者 ICAM-1(rs5498)的纯合变异基因型(GG)频率低于非狭窄非穿透型CD患者(0.00% vs. 12.32%， P＝0.001)。合并肛周病变的CD患者 ITGA4(rs6740847)的变异等位基因(G)和变异基因型(AG＋GG)的频率均高于无肛周病变的CD患者(40.28% vs. 30.77%， P＝0.049；72.22% vs. 51.75%， P＝0.004)。结论:ITGA4(rs7562325)基因变异可能是CD发病的风险因素。 ITGA4(rs6740847)基因变异可能与CD疾病活动度降低相关，却可能是结肠受累和肛周病变的风险因素。 ICAM-1(rs5498)基因变异可能是CD疾病活动度增加和结肠受累的风险因素，却可能是狭窄或穿透的保护因素。此外， ITGA4(rs6740847)基因变异和 ICAM-1(rs5498)基因变异可能均与CD疾病早发相关。
其他摘要	Objective:To assess the association between the polymorphisms of integral protein α4 ( ITGA4) and intercellular adhesion molecule 1 ( ICAM-1) genesand the risk and clinicopathological characteristics of Crohn′s disease (CD) among Chinese patients. Methods:From January 2010 to January 2021, a total of 215 CD patients and 529 gender- and age-matched healthy controls were enrolled from the Second Affiliated Hospital of Wenzhou Medical University as the study subjects. Genotypes of ITGA4 (rs6740847, rs7562325) and ICAM-1 (rs5498) were determined by matrix-assisted laser desorption ionization-time of flight mass spectrometry. Harvey-Bradshaw Index (HBI) was applied to assess the disease activity of CD, and the patients were further divided into subgroups based on the Montreal Classification Criteria of CD. Unconditional logistic regression was employed to analyze the distribution of ITGA4 (rs6740847, rs7562325) and ICAM-1 (rs5498) polymorphisms between the patients and healthy controls and their association with the clinicopathological characteristics of the patients. Results:The frequencies of T allele and CT+ TT genotypes of ITGA4 (rs7562325) were higher in CD patients than the healthy controls (40.70% vs. 31.57%, P=0.001; 62.79% vs. 54.36%, P=0.042). The G variant and AG+ GG genotypes of ITGA4 (rs6740847) were less common in patients with moderately to severely active CD compared with those with mildly active CD (31.18% vs. 51.72%, P=0.002; 55.91% vs. 75.86%, P=0.042). However, the opposite conclusion was drawn for the G allele (G) and AG+ GG genotypes of ICAM-1 (rs5498) (31.45% vs. 17.24%, P=0.027; 54.30% vs. 31.04%, P=0.020). Compared with patients with terminal ileal or ileocolic CD, G allele and AG+ GG genotypes of ITGA4 (rs6740847) were more prevalent in patients with colonic CD (55.26% vs. 29.38%, P<0.000 1; 84.21% vs. 53.11%, P<0.000 1). The same conclusion could also be drawn for the G allele and AG+ GG genotypes of ICAM-1 (rs5498) (42.11% vs. 26.84%, P=0.008; 73.69% vs. 46.33%, P=0.002). The frequency of homozygous GG genotype of ICAM-1 (rs5498) was lower in patients with stricturing and penetrating CD than those with non-stricturing and non-penetrating CD (0.00% vs. 12.32%, P=0.001). The G allele and AG+ GG genotypes of the ITGA4 (rs6740847) were more common in patients with perianal lesions than those without (40.28% vs. 30.77%, P=0.049; 72.22% vs. 51.75%, P=0.004). Conclusion:Variants of the ITGA4 (rs7562325) may be a risk factor for CD, whilst those of the ITGA4 (rs6740847) may be associated with the decline of disease activity and risk for colon involvement and perianal lesions. Variants of the ICAM-1 (rs5498) may increase the risk of disease activity and colonic involvement in CD patients, however, it may be a protective factor for stenosis and penetration. In addition, variants of the ITGA4 (rs6740847) and ICAM-1 (rs5498) may be associated with the early onset of CD.
资助项目	浙江省自然科学基金(LY18H030009);浙江省医药卫生科技计划(2021KY802、2021KY803);浙江省中医药科技计划(2019ZB075);温州市科技计划(Y20190603、Y20220031);贺林院士工作站科研基金(19331101、19331104)。
出版者	Chinese Medical Journals Publishing House Co.Ltd
ISSN	1003-9406
卷号	41 期号:2 页码:157-166
DOI	10.3760/cma.j.cn511374-20221103-00755
页数	10
收录类别	万方 ; 维普 ; SCOPUS ; CSCD ; ISTIC ; 北大核心
URL	查看原文
PubMed ID	38311553
SCOPUSEID	2-s2.0-85184084675
通讯作者地址	[Jiang, Yi]Department of Gastroenterology,Yuying Children's Hospital,The Second Affiliated Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,325000,China
Scopus学科分类	Medicine (all)
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/214891
专题	附属第二医院附属第二医院_消化内科第二临床医学院、附属第二医院、育英儿童医院附属第二医院_内科
作者单位	温州医科大学附属第二医院、育英儿童医院消化内科，温州　325000
第一作者单位	附属第二医院; 第二临床医学院，附属第二医院、育英儿童医院; 消化内科; 内科
通讯作者单位	第二临床医学院，附属第二医院、育英儿童医院; 附属第二医院
第一作者的第一单位	附属第二医院
推荐引用方式 GB/T 7714	张顶力,吴昊,邵晓晓,等. 整联蛋白α4和细胞间黏附分子1基因多态性与克罗恩病发病风险及其临床病理特征的相关性[J]. 中华医学遗传学杂志,2024,41(2):157-166.
APA	张顶力, 吴昊, 邵晓晓, 肖慧盈, & 蒋益. (2024). 整联蛋白α4和细胞间黏附分子1基因多态性与克罗恩病发病风险及其临床病理特征的相关性. 中华医学遗传学杂志, 41(2), 157-166.
MLA	张顶力,et al."整联蛋白α4和细胞间黏附分子1基因多态性与克罗恩病发病风险及其临床病理特征的相关性".中华医学遗传学杂志 41.2(2024):157-166.