Role of matrix metalloproteinase,tissue inhibitor of metalloproteinase and tumor necrosis factor-α single nucleotide gene polymorphisms in inflammatory bowel disease

作     者：Martin JW Meijer Marij AC Mieremet-Ooms Ruud A van Hogezand Cornelis BHW Lamers Daniel W Hommes Hein W Verspaget 

作者机构：Department of Gastroenterology and HepatologyLeiden University Medical CenterLeidenThe Netherlands 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2007年第13卷第21期

页      面：2960-2966页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：grant WS98-17 from the Netherlands Digestive Diseases Foundation 

主　　题：肠炎 单核苷酸多态性 抑制剂 治疗 溃疡性结肠炎 

摘      要：AIM:To study the (functional) relevance of single nucleotide polymorphisms (SNPs) in genes encoding matrix metalloproteinases (MMP)-1,-2,-3,-9,tissue inhibitors of metalloproteinases (TIMP)-1,-2 and tumor necrosis factor (TNF)-α in the etiopathogenesis of inflammatory bowel diseases (IBD),that may enhance susceptibility and/or disease severity. METHODS:Genomic DNA from 134 Crohn s disease (CD),111 ulcerative colitis (UC) patients and 248 control subjects was isolated from resected intestinal tissue or blood. Allelic composition at SNP loci was determined by PCR-RFLP or tetra primer ARMS PCR. RESULTS:The TIMP-1 genotype TT in women and T in men at SNP +372 T/C was found to increase CD susceptibility (39% vs 23.8%,P=0.018 and 67.9% vs 51.6%,P=0.055,respectively),while women with this genotype were less prone to development of fistulae during follow-up (41.4% vs 68.3%,P=0.025). Male IBD or CD patients carrying the TIMP-1 +372 T-allele expressed lower levels of TIMP-1 in surgically resected macroscopically inflamed tissue (0.065 P 0.01). The 5T5T genotype at MMP-3 SNP -1613 5T/6T increased the chance of stenotic complications in CD during follow-up (91.2% vs 71.8%,P = 0.022) but seemed to protect against colonic involvement of this disease at first endoscopic/radiologic examination (35.3% vs 59.5%,P=0.017). CONCLUSION:Allelic composition at the examinedSNPs in genes coding for TIMP-1 and MMP-3 affect CD susceptibility and/or phenotype,i.e.,fistulizing disease,stricture pathogenesis and first disease localisation. These findings reinforce the important role of these proteins in IBD.