Xiucai Lan1,2, Xiuhua Lan3, Ying Chang1,2, Xiaomin Zhang1,2, Jing Liu1,2, Vikash Vikash4, Wei Wang5, Meifang Huang1,2, Xiaobing Wang1,2, Feng Zhou1,2, Liping Chen1,2, Qiu Zhao1,2. 1. Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China. 2. The Hubei Clinical Center & Key Laboratory of Intestinal & Colorectal Diseases, Wuhan, China. 3. Pathology Department, Center for Drug Safety Evaluation and Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China. 4. Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China. 5. Department of Gastroenterology, The Sixth Affiliated Hospital of Zhongshan University, Guangzhou, China.
Abstract
BACKGROUND/AIMS: To investigate the associations between the rs1250569 (zinc finger MIZ-type containing 1, ZMIZ1), rs1042522 (tumour protein p53, TP53), and rs10114470 (tumour necrosis factor-like cytokine 1A, TL1A) polymorphisms and the development of inflammatory bowel disease (IBD) in a Chinese (Han) population. We analysed the expression of genes that predispose patients to Crohn's disease (CD) and ulcerative colitis (UC). METHODS: A total of 381 IBD patients and 517 healthy controls were recruited into our study. Polymorphisms at the three loci were genotyped using polymerase chain reaction-ligation detection reactions (PCR-LDR). Genotype-phenotype correlations were analysed. Blood and gut samples were obtained and analysed using quantitative real-time PCR (qRT-PCR), western blot analysis, and immunohistochemistry to investigate the mRNA and protein levels and in situ expression of genes found to predispose patients to IBD. Furthermore, the expression of susceptible genes was further verified using a mouse dextran sulphate sodium (DSS)-induced acute colitis model. RESULTS: No significant association was detected between rs1250569 and rs1042522 genotypes and CD or UC susceptibility. However, the frequency of allele A of rs1250569 was much higher in CD patients than that in healthy controls (55.03% vs. 48.48%, respectively; p = 0.044). The mutation rates at rs10114470 were dramatically lower at both the genotype and allele level in patients than those in healthy controls (p = 0.002 at both the genotype and allele level). Additionally, increased ZMIZ1 and TL1A levels were detected in intestinal samples obtained from both IBD patients and DSS-treated mice. CONCLUSION: rs1250569 (ZMIZ1) and rs10114470 (TL1A) are two novel loci that indicate susceptibility to IBD in Han-Chinese patients. Consistent with previous studies, TL1A expression levels were higher in Chinese Han IBD patients and DSS-treated mice. Most importantly, we found that ZMIZ1 expression was markedly higher in both IBD patients and mice with experimentally induced colitis, suggesting that ZMIZ1 plays important roles in the pathogenesis of IBD.
BACKGROUND/AIMS: To investigate the associations between the rs1250569 (zinc finger MIZ-type containing 1, ZMIZ1), rs1042522 (tumour protein p53, TP53), and rs10114470 (tumour necrosis factor-like cytokine 1A, TL1A) polymorphisms and the development of inflammatory bowel disease (IBD) in a Chinese (Han) population. We analysed the expression of genes that predispose patients to Crohn's disease (CD) and ulcerative colitis (UC). METHODS: A total of 381 IBDpatients and 517 healthy controls were recruited into our study. Polymorphisms at the three loci were genotyped using polymerase chain reaction-ligation detection reactions (PCR-LDR). Genotype-phenotype correlations were analysed. Blood and gut samples were obtained and analysed using quantitative real-time PCR (qRT-PCR), western blot analysis, and immunohistochemistry to investigate the mRNA and protein levels and in situ expression of genes found to predispose patients to IBD. Furthermore, the expression of susceptible genes was further verified using a mousedextran sulphate sodium (DSS)-induced acute colitis model. RESULTS: No significant association was detected between rs1250569 and rs1042522 genotypes and CD or UC susceptibility. However, the frequency of allele A of rs1250569 was much higher in CDpatients than that in healthy controls (55.03% vs. 48.48%, respectively; p = 0.044). The mutation rates at rs10114470 were dramatically lower at both the genotype and allele level in patients than those in healthy controls (p = 0.002 at both the genotype and allele level). Additionally, increased ZMIZ1 and TL1A levels were detected in intestinal samples obtained from both IBDpatients and DSS-treated mice. CONCLUSION:rs1250569 (ZMIZ1) and rs10114470 (TL1A) are two novel loci that indicate susceptibility to IBD in Han-Chinese patients. Consistent with previous studies, TL1A expression levels were higher in Chinese Han IBDpatients and DSS-treated mice. Most importantly, we found that ZMIZ1 expression was markedly higher in both IBDpatients and mice with experimentally induced colitis, suggesting that ZMIZ1 plays important roles in the pathogenesis of IBD.