Erschienen in:
01.11.2007
Clarithromycin Resistance, Tumor Necrosis Factor Alpha Gene Polymorphism and Mucosal Inflammation Affect H. pylori Eradication Success
verfasst von:
Carlo-Federico Zambon, Michela Fasolo, Daniela Basso, Anna D’Odorico, Alessia Stranges, Filippo Navaglia, Paola Fogar, Eliana Greco, Stefania Schiavon, Andrea Padoan, Elisa Fadi, Giacomo Carlo Sturniolo, Mario Plebani, Sergio Pedrazzoli
Erschienen in:
Journal of Gastrointestinal Surgery
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Ausgabe 11/2007
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Abstract
Several bacterial and host-related factors concur in causing Helicobacter pylori eradication failure. We ascertained the role of bacterial virulence genes (cagA, vacA), clarithromycin resistance [ClaR, 23S ribosomal RNA (rRNA) mutations], host polymorphism of CYP2C19 (polyphosphoinositide, PPI, metabolism) and of the cytokines IL-1B-31C>T, IL-1RN VNTR, IFN-γ+874A>T, TNF-α-1031T>C, TNF-α-857C>T, TNF-α-376G>A, TNF-α-308G>A, TNF-α-238G>A, IL-10-1082A>G, IL-10-819C>T, IL-10-592C>A, IL-12A+6686G>A, IL-12B+15485A>C. Two groups of H. pylori-infected and H. pylori-treated patients were retrospectively identified: 45 not eradicated and 57 eradicated. Treatment failure was significantly correlated with ClaR (all resistant strains in non-eradicated patients); with TNF-α-238, IL10-819, IL10-592, IL-12B+15485 single nucleotide polymorphism (SNP); with IL10 ATA/ATA haplotype; and with antral inflammatory grade. On considering ClaS-infected patients only, logistic regression analysis (eradication = dependent; TNF-α-238, IL12B + 15485 genotypes, IL10 ATA/ATA as present or absent, antral gastritis grade = covariates) confirmed as significantly correlated with eradication antral gastritis grade only (Exp(B) = 6.48; 95% CI, 1.2–35.01). In conclusion, the bacterial determinant causing triple therapy failure is clarithromycin resistant, being virulence genes not involved. The host related factors that favor eradication are those linked to inflammation: a higher inflammatory infiltrate in the mucosa, possibly favored by genotypes able to down regulate the anti-inflammatory cytokine response, enhance the chance of eradication success.