IL-4 -588C>T polymorphism and IL-4 receptor alpha [Ex5+14A>G; Ex11+828A>G] haplotype concur in selecting H. pylori cagA subtype infections.
BACKGROUND
The Th2 cytokine IL-4 might limit H. pylori associated gastric inflammation and favour H. pylori clearance. The aim of the study was to verify whether IL-4 -588C>T SNP, or two SNPs of the gene coding the alpha chain of IL-4 receptor (IL-4RA Ex5+14A>G, IL-4RA Ex11+828A>G) considered singly or as haplotypes, are correlated with H. pylori virulence genes or H. pylori associated diseases.


METHODS
We studied 144 patients with non-cardia gastric cancer (NCGC)(41/50 with present or past H. pylori infection), 75 with duodenal ulcer (DU)(66 H. pylori infected) and 171 with gastritis (CG)(107 H. pylori infected). cagA gene was present in 24/28 NCGC, 45/59 DU and 56/107 CG.


RESULTS
All SNPs were in Hardy-Weinberg equilibrium. IL-4RA haplotypes frequencies were estimated using Arlequin software. Neither the SNPs nor the IL-4RA haplotype correlated with disease diagnosis, H. pylori infection, degree of mucosal inflammation or intestinal metaplasia. IL-4 -588T allele (OR=3.69, 95% CI:1.34-10.16) and IL-4RA GA haplotype (p<0.05) enhanced the risk for cagA positive infections. IL-4RA GA haplotype correlated with IL-4 protein levels in H. pylori infected gastric mucosa.


CONCLUSIONS
IL-4 and IL-4RA gene polymorphisms concur in selecting the H. pylori infecting strain, probably influencing the IL-4 signalling pathway.
Zambon
Carlo-Federico
CF
Department of Medical and Surgical Sciences, University of Padova, Italy.
Basso
Daniela
D
Marchet
Alberto
A
Fasolo
Michela
M
Stranges
Alessia
A
Schiavon
Stefania
S
Navaglia
Filippo
F
Greco
Eliana
E
Fogar
Paola
P
Falda
Alessandra
A
D'Odorico
Anna
A
Rugge
Massimo
M
Nitti
Donato
D
Plebani
Mario
M
D000328:Adult; D000368:Aged; D000942:Antigens, Bacterial / Q000235:genetics*; D001426:Bacterial Proteins / Q000235:genetics*; D005260:Female; D006239:Haplotypes; D016481:Helicobacter Infections / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D015847:Interleukin-4 / Q000235:genetics*; D053662:Interleukin-4 Receptor alpha Subunit / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C504000:IL4R protein, human; D053662:Interleukin-4 Receptor alpha Subunit; C080866:cagA protein, Helicobacter pylori; D015847:Interleukin-4