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.
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.
基金
grant WS98-17 from the Netherlands Digestive Diseases Foundation
关键词
肠炎
单核苷酸多态性
抑制剂
治疗
溃疡性结肠炎
Crohn＇s disease
Ulcerative colitis
Matrix metalloproteinases
Inhibitors of matrix metalloproteinases
Single nucleotide gene polymorphisms
