IL1B and IL1RN polymorphic genes and Helicobacter pylori cagA strains decrease the risk of reflux esophagitis

Gastroenterology. 2004 Jul;127(1):73-9. doi: 10.1053/j.gastro.2004.03.069.


Background & aims: Proinflammatory interleukin (IL)-1 gene polymorphisms associated with high levels of IL-1beta activity increase the risk for hypochlorhydria and distal gastric carcinoma. The aim of this study was to evaluate whether carriers of these polymorphic genes are protected against gastroesophageal reflux disease (GERD). TNFA-308 polymorphisms were also studied.

Methods: We prospectively evaluated 385 patients without gastric cancer and peptic ulcer. Of these patients, 383 (98 with GERD and 285 controls) were successfully genotyped for all cytokines studied. The cagA status of Helicobacter pylori isolates was determined by polymerase chain reaction (PCR). IL1B-511/-31, IL1RN, and TNFA-308 polymorphisms were genotyped by PCR, PCR/restriction fragment length polymorphism, or PCR/confronting 2-pair primers. Histologic gastritis was assessed according to the updated Sydney system. The role of the proinflammatory cytokine genotypes in the genesis of GERD was evaluated before and after stratification by H. pylori status in logistic regression models controlling for confounding factors.

Results: IL1B-31 (a near-complete linkage disequilibrium between polymorphism at -31 and -511 was found) and IL1RN*2 allele polymorphisms were associated with GERD. After stratification, in the group of H. pylori-positive patients, cagA-positive status, IL1B-31 polymorphic alleles, IL1RN*2 alleles, and the degree of corpus gastritis were negatively associated with GERD. In the H. pylori-negative group, IL1B-31C/C genotype was inversely associated with GERD even after adjustment for age and sex.

Conclusions: This study provides evidence supporting the independent protective role of cagA-positive H. pylori status and IL1B and ILRN allele polymorphisms against GERD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, Bacterial / genetics*
  • Bacterial Proteins / genetics*
  • Gastroesophageal Reflux / complications
  • Gastroesophageal Reflux / genetics*
  • Gastroesophageal Reflux / prevention & control
  • Helicobacter Infections / complications
  • Helicobacter Infections / genetics*
  • Heterozygote
  • Humans
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1 / genetics*
  • Polymorphism, Genetic
  • Prospective Studies
  • Risk
  • Sialoglycoproteins / genetics*
  • Tumor Necrosis Factor-alpha / genetics


  • Antigens, Bacterial
  • Bacterial Proteins
  • IL1RN protein, human
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • Sialoglycoproteins
  • Tumor Necrosis Factor-alpha
  • cagA protein, Helicobacter pylori