V75Q576 IL-4Ra variant and IL-4-588T allele favor cagA-positive Helicobacter pylori infections

Interleukin-4 (IL-4), which acts by binding to its receptor, IL-4Ra, affects the immune system and can modify gastric acid secretion. Our aim was to elucidate the relationships between IL-4 and IL-4Ra genetic polymorphisms, considered singly or as haplotypes, and H. pylori infection or H. pylori associated diseases. IL-4 -588CT, IL-4R 148AG, IL-4R 1652AG were assayed in 170 patients with gastritis (107 Hp+), 75 duodenal ulcer (66 Hp+), 144 non-cardia gastric cancer (91 Hp+). H. pylori ureA and cagA were PCR amplified from mucosal DNA; gastritis grade was assessed (H&E). Haplotypes were estimated by Arlequin software. Allele frequencies were: -588C=0.86, -588T=0.14, 148A=0.55, 148G=0.45, 1652A=0.84, 1652G=0.16. All SNPs were in Hardy- Weinberg equilibrium. IL-4 or IL-4R single genotypes were neither correlated with disease diagnosis nor with H. pylori infection or gastritis grade. Considering gastritis patients IL-4 –588T allele was cagA associated (X2=9.12, p<0.01). IL-4R haplotype frequencies, considering the 148AG and 1652AG loci, were: AA=48.6%, AG=6.0%, GA=35.2%, GG=10.2%. The GA haplotype (V75Q576 aminoacids combined in the same protein) was correlated with cagA (X2=4.42, p<0.05). After patients with or without at least a GA haplotype were subdivided into different groups, the association between cagA and IL-4 –588T was confirmed only in those without GA haplotype (X2=4.04, p<0.05). Conclusions. IL-4R GA haplotype and IL-4 –588T allele favour cagA infections. The V75Q576 combination resulting from this haplotype may affects receptor functioning while IL-4 –588T allele may affect the amount of the secreted cytokine. These genetic variants may modulate IL-4 effect on gastric acid secretion and/or Th2 response.