Association between Helicobacter pylori cagA-related genes and clinical outcomes in Colombia and Japan

Masahide Watada,Yoshio Yamaoka,Kazunari Murakami,Osamu Matsunari,Seiji Shiota,Rumiko Suzuki,Toshio Fujioka

doi:10.1186/1471-230x-11-141

Abstract

BackgroundSpecific genotypes of several virulence factors of Helicobacter pylori (eg, cagA-positive, vacA s1, oipA "on" and babA-positive) have been reported to be predictors of severe clinical outcomes. Importantly, the presence of these genotypes correlates with each other. We hypothesized that novel virulence genes correlate with the presence of cagA. Therefore, we aimed to find novel candidate virulence genes that correlate with cagA and examined the association of these genes with clinical outcomes in Colombian and Japanese populations.MethodscagA-associated genes were selected based on previous H. pylori genome microarray data. A total of 343 strains (174 from Colombia and 169 from Japan) were examined for the status of cagA, vacA, and candidate genes by polymerase chain reaction and dot blot.ResultsMicroarray data showed that 9 genes were significantly correlated with the presence of cagA. Among the 9 genes, the functions of 4 were known, and we selected these 4 genes as candidate genes (hp0967, jhp0045, jhp0046, and jhp0951). The prevalences of cagA, vacA s1/m1 genotype, and hp0967 were significantly higher in Japan than Colombia, whereas those of jhp0045 and jhp0046 were more prevalent in Colombia than Japan. The prevalences of jhp0045 and jhp0046 in cagA-positive cases of gastric cancer were significantly higher than those from gastritis in Colombia (P = 0.015 and 0.047, respectively). In contrast, the prevalence of 4 candidate genes was independent of clinical outcomes in Japan.Conclusionsjhp0045 and jhp0046 might be novel markers for predicting gastric cancer in cagA-positive cases in Colombia, but not in Japan.

Highlights

Specific genotypes of several virulence factors of Helicobacter pylori have been reported to be predictors of severe clinical outcomes
Because hp1426 was reported in both reports, a total of 37 genes were selected as candidate genes, as shown in additional file 1
Our study revealed that jhp0045 and jhp0046 were independent discriminating factors for gastric cancer (GC) from gastritis in cagA-positive cases in Colombia

Summary

Introduction

Specific genotypes of several virulence factors of Helicobacter pylori (eg, cagA-positive, vacA s1, oipA “on” and babA-positive) have been reported to be predictors of severe clinical outcomes. We aimed to find novel candidate virulence genes that correlate with cagA and examined the association of these genes with clinical outcomes in Colombian and Japanese populations. Several epidemiological studies have shown that H. pylori infection is linked to severe gastritis-associated diseases, including peptic ulcer and gastric cancer (GC) [1]. In addition to environmental factors (eg, diet) and host factors, virulence factors of H. pylori, such as cagA, vacA, oipA, babA, hopQ, and homA/B, have been demonstrated to be predictors of gastric atrophy, intestinal metaplasia, and severe clinical outcomes [4,5,6,7,8,9,10]. CagA protein is believed to have oncogenic potential [12,13], and cagA-positive strains are reported to be associated with severe clinical outcomes [14]

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