Pro- and anti-inflammatory cytokines gene polymorphisms and Helicobacter pylori infection: interactions influence outcome.
The aim of this study was to evaluate whether there was any correlation between Helicobacter pylori-associated diseases and (1) H. pylori virulence genes or (2) IL-1B, IL-1RN, IFN-G, TNF-A, IL-10 genetic polymorphisms. Patients with non-cardia gastric cancer (NCGC, n=129) or benign gastroduodenal diseases (n=792) were studied. IL-1RN intron 2 VNTR polymorphism (PCR), IL-1B -31 C/T (RFLP), the SNPs of IFN-G (+874 A/T), TNF-A (-1031 C/T, -857 C/T, -376 A/G, -308 A/G, -238 A/G), IL-10 (-1082 A/G, -819 C/T, -592 A/C) (Taqman chemistry) were studied. cagA, s1 and m1 vacA, were PCR amplified. Duodenal ulcer was more frequent in TNF-A -857 TT and in IL-1RN 1,2 subjects. TNF-A -857 TT genotype was also correlated with gastric ulcer. IL-10 -819 TT genotype was associated with intestinal metaplasia and NCGC. Antral inflammation was associated with TNF-A -1031 TT, while corpus activity with IL-10 -819 CC. H. pylori infection was associated with TNF-A -308 AG genotype, while IFN-G +874 AA genotype was associated with cagA. In conclusion, among host genetic factors contributing to H. pylori disease outcome, IFN-G +874 AA genotype favors cagA positive infections, TNF-A -857 TT duodenal ulcer while IL-10 -819 TT intestinal metaplasia and NCGC.
Zambon
Carlo-F
CF
Department of Medical and Surgical Sciences, University of Padua, Via Giustiniani 2, 35128 Padua, Italy. biolmol@unipd.it
Basso
Daniela
D
Navaglia
Filippo
F
Belluco
Claudio
C
Falda
Alessandra
A
Fogar
Paola
P
Greco
Eliana
E
Gallo
Nicoletta
N
Rugge
Massimo
M
Di Mario
Francesco
F
Plebani
Mario
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016207:Cytokines / Q000235:genetics*; D004381:Duodenal Ulcer / Q000209:etiology / Q000235:genetics; D005260:Female; D005756:Gastritis / Q000209:etiology / Q000235:genetics; D005787:Gene Frequency; D005838:Genotype; D016481:Helicobacter Infections / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D016480:Helicobacter pylori / Q000235:genetics* / Q000472:pathogenicity; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D007410:Intestinal Diseases / Q000209:etiology / Q000235:genetics; D007558:Italy; D008297:Male; D008679:Metaplasia / Q000209:etiology / Q000235:genetics; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D013274:Stomach Neoplasms / Q000209:etiology / Q000235:genetics; D013276:Stomach Ulcer / Q000209:etiology / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D014774:Virulence / Q000235:genetics
D016207:Cytokines; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10