The Effects of Genetic Polymorphisms of IL-6, IL-8, and IL-10 on Helicobacter pylori-induced Gastroduodenal Diseases in Korea

Abstract

Background: The genes that encode proinflammatory and antiinflammatory cytokines are good candidate markers of host susceptibility to gastroduodenal disease. The present study was performed to evaluate whether or not the genetic polymorphisms of IL-6, IL-8, and IL-10 are associated with gastroduodenal disease in the Korean population. Methods: This study enrolled 1187 patients, including controls, those with gastric cancer (GC), benign gastric ulcer (BGU), and duodenal ulcer patients. Six polymorphisms were genotyped, 3 of IL-10 (at -592, -819, and -1082), 1 of IL-8 (at -251), and 2 of IL-6 (at -174 and -572) by polymerase chain reaction-restriction fragment length polymorphism analysis. Results: The frequency of IL-10-1082 G carriers was higher in cases of a diffuse type GC [odds ratio (OR) 1.81 95% confidence interval (CI): 1.0-3.1, P = 0.041] or BGU (OR 1.6, 95% Cl: 1.0-2.5, P = 0.040), than in the control group regardless of Helicobacter pylori infection. The IL-8-251 A/A genotype was more common in H. pylori-positive patients with GC (OR 2.0, 95% Cl: 1.2-3.6, P = 0.013) or BGU (OR 2.7 95% Cl: 1.5-4.8, P = 0.001) than in H. pylori-positive controls. In addition, the frequencies of IL-6-572 G/G (OR 0.3, 95% Cl: 0.1-0.9 P = 0.027) and of G carriers (OR 0.5, 95% Cl: 0.4-0.8, P = 0.003) were lower in H. pylori-positive duodenal ulcer patients than in H. pylori-positive controls. IL-10-592 C/C (OR 0.4, 95% Cl: 0.2-0.9. P = 0.028) was an independent factor associated with a decreased risk of the intestinal type of GC by multivariate analysis. Furthermore, a synergistic effect was observed between IL-10-592 A/A and IL-8-251 A/A with respect to the development of GC or BGU. Conclusions: These results suggest that the genetic polymorphisms of these 3 inflammation-related cytokines, IL-10, IL-8. and IL-6, are associated with the development of H. pylori-associated gastroduodenal disease.