Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Idaigaoka, Hasama-machi, Yufu-City, Japan.
BMC Gastroenterol. 2011 Dec 22;11:141. doi: 10.1186/1471-230X-11-141.
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. 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.
cagA-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.
Microarray 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.
jhp0045 and jhp0046 might be novel markers for predicting gastric cancer in cagA-positive cases in Colombia, but not in Japan.
已报道幽门螺杆菌(Helicobacter pylori)的几种毒力因子(例如 cagA 阳性、vacA s1、oipA“开启”和 babA 阳性)的特定基因型是严重临床结局的预测因子。重要的是,这些基因型的存在相互关联。我们假设新的毒力基因与 cagA 的存在相关。因此,我们旨在寻找与 cagA 相关的新型候选毒力基因,并在哥伦比亚和日本人群中研究这些基因与临床结局的关联。
根据先前的幽门螺杆菌基因组微阵列数据选择 cagA 相关基因。通过聚合酶链反应和斑点印迹法检测 343 株(174 株来自哥伦比亚,169 株来自日本)菌株 cagA、vacA 和候选基因的状态。
微阵列数据分析显示,9 个基因与 cagA 的存在显著相关。在这 9 个基因中,有 4 个的功能是已知的,我们选择了这 4 个基因作为候选基因(hp0967、jhp0045、jhp0046 和 jhp0951)。日本的 cagA、vacA s1/m1 基因型和 hp0967 的流行率明显高于哥伦比亚,而 jhp0045 和 jhp0046 的流行率在哥伦比亚则高于日本。在哥伦比亚,胃癌病例中 cagA 阳性者的 jhp0045 和 jhp0046 的流行率显著高于胃炎患者(分别为 P = 0.015 和 0.047)。相比之下,日本候选基因 4 的流行率与临床结局无关。
jhp0045 和 jhp0046 可能是预测哥伦比亚 cagA 阳性病例胃癌的新型标志物,但在日本并非如此。