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。 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 ofICAM-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.
Association ofITGA4 andICAM-1 gene polymorphisms with the risk and clinicopathological characteristics of Crohn′s disease
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 ofICAM-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.
Crohn′s diseaseIntegral protein α4Intercellular adhesion molecule 1Genetic polymorphism
万方数据
