BACKGROUND AND AIMS: Matrix metalloproteinases (MMPs) are a family of enzymes that degrade most of the macromolecules making up the extracellular matrix. H. pylori infection increases the secretion of MMPs in the gastric mucosa leading to severe mucosal damage. The aim of this study was to investigate if genetic variants in MMPs involved in the inflammatory response to H. pylori could predispose patients with chronic H. pylori infection to develop gastric ulcer disease. METHODS: A total of 599 H. pylori-infected patients undergoing gastroscopy were genotyped for 20 SNPs covering the MMP-1, -3, -7, and -9 genes by TaqMan technology. Haplotype and single marker analysis was conducted to assess associations with gastric ulcer disease. RESULTS: Carriage of allele G of the functional promoter variant MMP-7-181 was significantly associated with gastric ulcer conferring a 1.6-fold increased risk (95% CI: 1.0-2.6, p = 0.037). In addition, carriage of allele A of a coding SNP in exon 6 of MMP-9 confers a 2.4-fold increased risk (95% CI: 1.0-2.6, p = 0.013) for gastric ulcer. CONCLUSION: The level of association found in this study is in agreement with the nature of a complex genetic disease. Genetic variations in the MMP-7 and -9 gene may be part of a complex genetic risk profile to develop gastric ulcer in chronic H. pylori infection. Further studies are warranted to elucidate the pathophysiological role of these genes in ulcerogenesis.
BACKGROUND AND AIMS: Matrix metalloproteinases (MMPs) are a family of enzymes that degrade most of the macromolecules making up the extracellular matrix. H. pyloriinfection increases the secretion of MMPs in the gastric mucosa leading to severe mucosal damage. The aim of this study was to investigate if genetic variants in MMPs involved in the inflammatory response to H. pylori could predispose patients with chronic H. pylori infection to develop gastric ulcer disease. METHODS: A total of 599 H. pylori-infectedpatients undergoing gastroscopy were genotyped for 20 SNPs covering the MMP-1, -3, -7, and -9 genes by TaqMan technology. Haplotype and single marker analysis was conducted to assess associations with gastric ulcer disease. RESULTS: Carriage of allele G of the functional promoter variant MMP-7-181 was significantly associated with gastric ulcer conferring a 1.6-fold increased risk (95% CI: 1.0-2.6, p = 0.037). In addition, carriage of allele A of a coding SNP in exon 6 of MMP-9 confers a 2.4-fold increased risk (95% CI: 1.0-2.6, p = 0.013) for gastric ulcer. CONCLUSION: The level of association found in this study is in agreement with the nature of a complex genetic disease. Genetic variations in the MMP-7 and -9 gene may be part of a complex genetic risk profile to develop gastric ulcer in chronic H. pylori infection. Further studies are warranted to elucidate the pathophysiological role of these genes in ulcerogenesis.
Authors: Seth R Ogden; Lydia E Wroblewski; Christiane Weydig; Judith Romero-Gallo; Daniel P O'Brien; Dawn A Israel; Uma S Krishna; Barbara Fingleton; Albert B Reynolds; Silja Wessler; Richard M Peek Journal: Mol Biol Cell Date: 2008-07-23 Impact factor: 4.138