Interferon gamma (IFNg) is associated with the development of Th-1-like, cell-mediated immune responses and plays a pivotal role in H. pylori-infected mucosa, as does the anti-inflammatory cytokine IL-10. Our aims were to ascertain whether the haplotypes made of 1, intron 1 IFNg +874TA SNP and CA repeat polymorphism or 2, IL-10–1082AG, −819CT and −592AC SNPs, influence H. pylori infection outcome and mucosal inflammation. H. pylori-infected patients were studied: 100 noncardia gastric cancer (NCGC), 28 duodenal ulcer (DU), and 71 chronic gastritis (CG). The haplotypes were estimated using the arlequin software version 2.000. Nine possible IFNg haplotypes were found, the most frequent being A-13 and T-12. DU was less frequent in T-12 haplotype with respect to NCGC (χ2 = 23.6, p < .01) or CG (χ2 = 17.0, p < .01). Three possible IL-10 haplotypes (−1082, −819, −592) were identified, ACC, ATA, GCC, none being correlated with disease diagnosis. None IFNg or IL-10 haplotypes were correlated with gastritis grade or intestinal metaplasia. Six possible IL-10 genotypes were inferred: ACC/ACC, ACC/ATA, ATA/ATA, ACC/GCC, ATA/GCC, GCC/GCC. The ATA/ATA was more frequent in NCGC with respect to CG (χ2 = 4.04, p < .05). The ATA/ATA was more frequent, whereas GCC/GCC was less frequent in CG patients than in those without intestinal metaplasia (χ2 = 11.04, p < .05). In conclusion, the IFNg high producer haplotype T-12 was protective for DU, probably because of the inhibitory effect on acid secretion of this cytokine. The attenuated IL-10 response of ATA/ATA low producers is probably implicated in the development of precancerous (intestinal metaplasia) and cancerous H. pylori-associated lesions.

Interferon gamma (IFNg) and interleukin-10 (IL-10) Haplotypes differently influence Helicobacter pylori infection outcome

ZAMBON, CARLO-FEDERICO;BASSO, DANIELA;BELLUCO, CLAUDIO;DI MARIO, FRANCESCO;FOGAR, PAOLA;GRECO, ELIANA;RUGGE, MASSIMO;PLEBANI, MARIO
2005

Abstract

Interferon gamma (IFNg) is associated with the development of Th-1-like, cell-mediated immune responses and plays a pivotal role in H. pylori-infected mucosa, as does the anti-inflammatory cytokine IL-10. Our aims were to ascertain whether the haplotypes made of 1, intron 1 IFNg +874TA SNP and CA repeat polymorphism or 2, IL-10–1082AG, −819CT and −592AC SNPs, influence H. pylori infection outcome and mucosal inflammation. H. pylori-infected patients were studied: 100 noncardia gastric cancer (NCGC), 28 duodenal ulcer (DU), and 71 chronic gastritis (CG). The haplotypes were estimated using the arlequin software version 2.000. Nine possible IFNg haplotypes were found, the most frequent being A-13 and T-12. DU was less frequent in T-12 haplotype with respect to NCGC (χ2 = 23.6, p < .01) or CG (χ2 = 17.0, p < .01). Three possible IL-10 haplotypes (−1082, −819, −592) were identified, ACC, ATA, GCC, none being correlated with disease diagnosis. None IFNg or IL-10 haplotypes were correlated with gastritis grade or intestinal metaplasia. Six possible IL-10 genotypes were inferred: ACC/ACC, ACC/ATA, ATA/ATA, ACC/GCC, ATA/GCC, GCC/GCC. The ATA/ATA was more frequent in NCGC with respect to CG (χ2 = 4.04, p < .05). The ATA/ATA was more frequent, whereas GCC/GCC was less frequent in CG patients than in those without intestinal metaplasia (χ2 = 11.04, p < .05). In conclusion, the IFNg high producer haplotype T-12 was protective for DU, probably because of the inhibitory effect on acid secretion of this cytokine. The attenuated IL-10 response of ATA/ATA low producers is probably implicated in the development of precancerous (intestinal metaplasia) and cancerous H. pylori-associated lesions.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11577/2526145
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