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 Helicobacter pylori infection or H. pylori-associated diseases. IL-4-588CT, IL-4R 148AG and IL-4R 1652AG were assayed in 170 patients with gastritis (107 H. pylori positive), 75 duodenal ulcer (66 H. pylori positive), 144 noncardia gastric cancer (91 H. pylori positive). H. pylori ureA and cagA were polymerase chain reaction amplified from mucosal DNA; gastritis grade was assessed (hematoxylin and eosin). Haplotypes were estimated using ARLEQUIN software. Allele frequencies were −588C = 0.86, −588T = 0.14, 148A = 0.55, 148G = 0.45, 1652A = 0.84, and 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 (χ2 = 9.12, p < .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 amino acids combined in the same protein) was correlated with cagA (χ2 = 4.42, p < .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 (χ2 = 4.04, p < .05). Conclusions. IL-4R GA haplotype and IL-4-588T allele favor cagA infections. The V75Q576 combination resulting from this haplotype may affect receptor functioning, whereas 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.