Gene polymorphisms of NOD1 and interleukin-8 influence the susceptibility to erosive esophagitis in Helicobacter pylori infected Japanese population

Helicobacter pylori (H. pylori) infection generally protects patients from erosive esophagitis through reduction of acid production due to gastric mucosal atrophy. However, there are H. pylori infected patients who still have erosive esophagitis. The reason for this discrepancy remains unclear. We have previously reported that polymorphisms in IL-8 promoter region influence the susceptibility of H. pylori related diseases. On the other hand, nucleotide-binding oligomerization domain 1 (NOD1) is known to play an important role in H. pylori infection. Hence, we hypothesized polymorphisms of these two molecules in H. pylori infected patients may influence the susceptibility to erosive esophagitis.Genomic DNA was extracted from 312 H. pylori infected Japanese, consisting of 110 patients with erosive esophagitis and 202 healthy controls. ND1+32656 T/GG and IL-8-251 A/T polymorphisms were genotyped by direct sequencing. ND1+32656 GG allele and IL-8-251 T/T allele increased the risk of erosive esophagitis with odds ratio (OR) of 1.9 (95% confidence interval (CI) 1.1-3.0, p= 0.013) and 1.7 (95% CI 1.1-2.8, p= 0.036), respectively. Combination of these two alleles increased the risk with OR of 3.2(95% CI 1.6-6.5, p= 0.001). In conclusion, ND1+32656 GG and IL-8-251 T/T allele may be associated with less reactivity to H. pylori infection, and may increase the risk of erosive esophagitis even in H. pylori infected Japanese population.