title: Clarithromycin resistance, tumor necrosis factor alpha gene polymorphism and mucosal inflammation affect H. pylori eradication success.
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 [Cla(R), 23S ribosomal RNA (rRNA) mutations], host polymorphism of CYP2C19 (polyphosphoinositide, PPI, metabolism) and of the cytokines IL-1B-31C>T, IL-1RN VNTR, IFN-gamma+874A>T, TNF-alpha-1031T>C, TNF-alpha-857C>T, TNF-alpha-376G>A, TNF-alpha-308G>A, TNF-alpha-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 Cla(R) (all resistant strains in non-eradicated patients); with TNF-alpha-238, IL10-819, IL10-592, IL-12B+15485 single nucleotide polymorphism (SNP); with IL10 ATA/ATA haplotype; and with antral inflammatory grade. On considering Cla(S)-infected patients only, logistic regression analysis (eradication = dependent; TNF-alpha-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.
authors.affiliation: Department of Medical and Surgical Sciences, University of Padova, Padova, Italy.
authors.forename: Carlo-Federico
authors.initials: CF
authors.lastname: Zambon
authors.forename: Michela
authors.initials: M
authors.lastname: Fasolo
authors.forename: Daniela
authors.initials: D
authors.lastname: Basso
authors.forename: Anna
authors.initials: A
authors.lastname: D'Odorico
authors.forename: Alessia
authors.initials: A
authors.lastname: Stranges
authors.forename: Filippo
authors.initials: F
authors.lastname: Navaglia
authors.forename: Paola
authors.initials: P
authors.lastname: Fogar
authors.forename: Eliana
authors.initials: E
authors.lastname: Greco
authors.forename: Stefania
authors.initials: S
authors.lastname: Schiavon
authors.forename: Andrea
authors.initials: A
authors.lastname: Padoan
authors.forename: Elisa
authors.initials: E
authors.lastname: Fadi
authors.forename: Giacomo Carlo
authors.initials: GC
authors.lastname: Sturniolo
authors.forename: Mario
authors.initials: M
authors.lastname: Plebani
authors.forename: Sergio
authors.initials: S
authors.lastname: Pedrazzoli
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000942:Antigens, Bacterial / Q000235:genetics; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D017291:Clarithromycin / Q000494:pharmacology*; D065731:Cytochrome P-450 CYP2C19; D004352:Drug Resistance, Microbial; D004359:Drug Therapy, Combination; D005260:Female; D005753:Gastric Mucosa; D005787:Gene Frequency; D016481:Helicobacter Infections / Q000188:drug therapy* / Q000235:genetics; D016480:Helicobacter pylori; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics; D010597:Pharmacogenetics; D017354:Point Mutation; D011110:Polymorphism, Genetic; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D014774:Virulence
chemical_list: D000900:Anti-Bacterial Agents; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D014409:Tumor Necrosis Factor-alpha; C074689:VacA protein, Helicobacter pylori; C080866:cagA protein, Helicobacter pylori; D016753:Interleukin-10; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D017291:Clarithromycin