The effects of genetic polymorphisms of IL-6, IL-8, and IL-10 on Helicobacter pylori-induced gastroduodenal diseases in Korea.
BACKGROUND
The genes that encode proinflammatory and anti-inflammatory 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) 1.8, 95% confidence interval (CI): 1.0-3.1, P=0.041] or BGU (OR 1.6, 95% CI: 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% CI: 1.2-3.6, P=0.013) or BGU (OR 2.7, 95% CI: 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% CI: 0.1-0.9, P=0.027) and of G carriers (OR 0.5, 95% CI: 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% CI: 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.
Kang
Jung Mook
JM
Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Kim
Nayoung
N
Lee
Dong Ho
DH
Park
Ji Hyun
JH
Lee
Mi Kyoung
MK
Kim
Joo Sung
JS
Jung
Hyun Chae
HC
Song
In Sung
IS
D000368:Aged; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D004381:Duodenal Ulcer / Q000208:ethnology / Q000235:genetics* / Q000276:immunology / Q000382:microbiology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D016481:Helicobacter Infections / Q000150:complications / Q000208:ethnology / Q000382:microbiology*; D016480:Helicobacter pylori / Q000302:isolation & purification*; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics*; D016209:Interleukin-8 / Q000235:genetics*; D007723:Korea; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D018570:Risk Assessment; D013274:Stomach Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000276:immunology / Q000382:microbiology; D013276:Stomach Ulcer / Q000208:ethnology / Q000235:genetics* / Q000276:immunology / Q000382:microbiology
C508606:CXCL8 protein, human; C508609:IL10 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D016753:Interleukin-10