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Journal of Gastrointestinal Surgery

, Volume 11, Issue 11, pp 1506–1514 | Cite as

Clarithromycin Resistance, Tumor Necrosis Factor Alpha Gene Polymorphism and Mucosal Inflammation Affect H. pylori Eradication Success

  • 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
Article

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.

Keywords

H. pylori Triple therapy Pharmacogenetics Cytokines Gene polymorphisms 

Abbreviations

ClaR

Clarithromycin resistant

ClaS

Clarithromycin sensitive

EM

extensive metabolizer

IM

intermediate metabolizer

MGB

DNA minor groove binder

PAI

pathogenicity island

PCR

polymerase chain reaction

PM

poor metabolizer

PPI

proton pump inhibitor

RFLP

restriction fragment length polymorphism

rRNA

ribosomal RNA

SNP

single nucleotide polymorphism

UBT

urea breath test

UM

ultrarapid metabolizer

VNTR

variable number of tandem repeats

6-FAM

6-carboxyfluorescin

Notes

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Copyright information

© The Society for Surgery of the Alimentary Tract 2007

Authors and Affiliations

  • Carlo-Federico Zambon
    • 1
  • Michela Fasolo
    • 2
  • Daniela Basso
    • 2
  • Anna D’Odorico
    • 3
  • Alessia Stranges
    • 2
  • Filippo Navaglia
    • 2
  • Paola Fogar
    • 1
  • Eliana Greco
    • 2
  • Stefania Schiavon
    • 2
  • Andrea Padoan
    • 2
  • Elisa Fadi
    • 2
  • Giacomo Carlo Sturniolo
    • 3
  • Mario Plebani
    • 2
  • Sergio Pedrazzoli
    • 1
    • 4
  1. 1.Department of Medical and Surgical SciencesUniversity of PadovaPadovaItaly
  2. 2.Department of Laboratory MedicineUniversity of PadovaPadovaItaly
  3. 3.Department of Surgical and Gastroenterological SciencesUniversity of PadovaPadovaItaly
  4. 4.Department of Medical and Surgical SciencesClinica Chirurgica IVPadovaItaly

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