Aftab Hafeza, Miftahussurur Muhammad, Subsomwong Phawinee, Ahmed Faruque, Khan A K Azad, Matsumoto Takashi, Suzuki Rumiko, Yamaoka Yoshio
Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Japan.
Department of Gastroenterology, Dhaka Medical College and Hospital, Dhaka, Bangladesh.
PLoS One. 2017 Aug 10;12(8):e0182947. doi: 10.1371/journal.pone.0182947. eCollection 2017.
Bangladesh has a population with a low gastric cancer risk but high prevalence of Helicobacter pylori infection. Several studies have examined virulence genes in H. pylori from Bangladesh. We analyzed cagA and vacA subtypes and their association with severe histology phenotypes, and analyzed population types among Bangladeshi strains. We included patients who underwent endoscopy in Dhaka. Sequences of virulence genes and seven housekeeping genes were obtained by next generation sequencing and confirmed by Sanger sequencing. We isolated 56 H. pylori strains from 133 patients, of which 73.2% carried cagA, and all were considered Western-type. Patients infected with cagA-positive strains had more severe histological scores than patients infected with cagA-negative strains. Among vacA s1 and m1 genotypes, the s1a (97.8%, 43/44) and m1c (28/30, 93.3%) genotypes were predominant. All strains containing s1 and m1 (30/56, 53.6%) also had i1, d1, and c1. In contrast, all strains containing the less-virulent genotypes s2 and m2 (12/56, 21.4%) also possessed i2, d2, and c2. Multivariate analysis indicated that subjects infected with vacA m1-genotype strains only had a significantly higher risk of antrum atrophy than patients infected with m2-genotype strains. Of the two main H. pylori populations in this study, hpAsia2 strains were associated with higher activity and inflammation in the antrum compared to hpEurope strains; however, only vacA s1m1i1d1c1 strains, independent of population type, were significantly associated with inflammation in the antrum, unlike the s2m2i2d2c2 genotype. In conclusion, Bangladeshi strains were divided into two main populations of different genotypes. The low incidence of gastric cancer in Bangladesh might be attributable to the high proportion of less-virulent genotypes, which may be a better predictor of gastric cancer risk than the ancestral origin of the H. pylori strains. Finally, the vacA m region may be a better virulence marker than other regions.
孟加拉国人口患胃癌风险较低,但幽门螺杆菌感染率较高。多项研究对来自孟加拉国的幽门螺杆菌毒力基因进行了检测。我们分析了cagA和vacA亚型及其与严重组织学表型的关联,并分析了孟加拉国菌株的群体类型。我们纳入了在达卡接受内镜检查的患者。通过下一代测序获得毒力基因和7个管家基因的序列,并通过桑格测序进行确认。我们从133例患者中分离出56株幽门螺杆菌菌株,其中73.2%携带cagA,且均被认为是西方型。感染cagA阳性菌株的患者组织学评分比感染cagA阴性菌株的患者更严重。在vacA s1和m1基因型中,s1a(97.8%,43/44)和m1c(28/30,93.3%)基因型占主导。所有含有s1和m1的菌株(30/56,53.6%)也具有i1、d1和c1。相比之下,所有含有毒力较低基因型s2和m2的菌株(12/56,21.4%)也具有i2、d2和c2。多因素分析表明,仅感染vacA m1基因型菌株的受试者胃窦萎缩风险显著高于感染m2基因型菌株的患者。在本研究的两种主要幽门螺杆菌群体中,与hpEurope菌株相比,hpAsia2菌株与胃窦更高的活性和炎症相关;然而,与s2m2i2d2c2基因型不同,只有vacA s1m1i1d1c1菌株,与群体类型无关,与胃窦炎症显著相关。总之,孟加拉国菌株分为两个不同基因型的主要群体。孟加拉国胃癌发病率较低可能归因于低毒力基因型的高比例,这可能比幽门螺杆菌菌株的祖先起源更能预测胃癌风险。最后,vacA m区域可能比其他区域是更好的毒力标志物。