Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu 879-5593, Japan.
Institute of Microbiology and Parasitology, IMPA, Faculty of Science, Autonomous University of Santo Domingo, Santo Domingo 10103, Dominican Republic.
World J Gastroenterol. 2020 Dec 7;26(45):7118-7130. doi: 10.3748/wjg.v26.i45.7118.
() colonizes the human stomach and is a major cause of peptic ulcer disease and gastric cancer. However, although the prevalence of is high in Africa, the incidence of gastric cancer is low, and this phenomenon is called to be African enigma. The CagA protein produced by is the most studied virulence factor. The carcinogenic potential of CagA is associated with the Glu-Pro-Ile-Tyr-Ala (EPIYA) patterns and CagA-multimerization (CM) motifs.
To better understand the EPIYA patterns and CM motifs of the gene.
Gastric mucosal biopsy specimens were obtained from 258 patients with dyspepsia living in the Dominican Republic, from which 120 strains were cultured. After the bacterial DNA extraction, the EPIYA pattern and CM motif genotypes were determined using a polymerase chain reaction-based sequencing. The population structure of the Dominican Republic strains was analyzed using multilocus sequence typing (MLST). Peptic ulcer disease and gastric cancer were identified endoscopy, and gastric cancer was confirmed by histopathology. Histological scores of the gastric mucosa were evaluated using the updated Sydney system.
All -positive strains carried the Western-type CagA according to the identified EPIYA patterns. Twenty-seven kinds of CM motifs were observed. Although the typical Western CM motif (FPLKRHDKVDDLSKVG) was observed most frequently, the typical East Asian CM motif (FPLRRSAAVNDLSKVG) was not observed. However, "FPLRRSAKVEDLSKVG", similar to the typical East Asian CM motif, was found in 21 strains. Since this type was significantly more frequent in strains classified as hpAfrica1 using MLST analysis ( = 0.034), we termed it Africa1-CM (Af1-CM). A few hpEurope strains carried the Af1-CM motif, but they had a significantly higher ancestral Africa1 component than that of those without the Af1-CM motif ( = 0.030). In 30 -positive strains, the "GKDKGPE" motif was observed immediately upstream of the EPIYA motif in the EPIYA-A segment, and there was a significant association between strains with the hpAfrica1 population and those containing the "GKDKGPE" motif ( = 0.018). In contrast, there was no significant association between the CM motif patterns and histological scores and clinical outcomes.
We found the unique African CM motif in Western-type CagA and termed it Africa1-CM. The less toxicity of this motif could be one reason to explain the African enigma.
幽门螺杆菌定植于人类胃部，是消化性溃疡病和胃癌的主要病因。然而，尽管幽门螺杆菌在非洲的流行率很高，但胃癌的发病率却很低，这种现象被称为非洲之谜。幽门螺杆菌产生的 CagA 蛋白是研究最多的毒力因子。CagA 的致癌潜力与 Glu-Pro-Ile-Tyr-Ala（EPIYA）模式和 CagA-多聚化（CM）基序有关。
更好地了解幽门螺杆菌基因的 EPIYA 模式和 CM 基序。
从 258 名居住在多米尼加共和国的消化不良患者的胃黏膜活检标本中培养了 120 株细菌。提取细菌 DNA 后，采用聚合酶链反应测序法确定 EPIYA 模式和 CM 基序基因型。采用多位点序列分型（MLST）分析多米尼加共和国菌株的种群结构。通过内镜检查确定消化性溃疡病和胃癌，通过组织病理学检查确诊胃癌。采用悉尼系统更新版评估胃黏膜的组织学评分。
所有阳性菌株根据鉴定的 EPIYA 模式均携带西方型 CagA。观察到 27 种 CM 基序。虽然最常观察到典型的西方 CM 基序（FPLKRHDKVDDLSKVG），但未观察到典型的东亚 CM 基序（FPLRRSAAVNDLSKVG）。然而，在 21 株菌中发现了类似于典型东亚 CM 基序的“FPLRRSAKVEDLSKVG”。由于该类型在 MLST 分析中被归类为 hpAfrica1 的菌株中更为常见（=0.034），因此我们将其命名为 Africa1-CM（Af1-CM）。少数 hpEurope 菌株携带 Af1-CM 基序，但它们的祖先 Africa1 成分明显高于没有 Af1-CM 基序的菌株（=0.030）。在 30 株阳性菌株中，EPIYA-A 段的 EPIYA 基序上游观察到“GKDKGPE”基序，携带 hpAfrica1 种群的菌株与含有“GKDKGPE”基序的菌株之间存在显著关联（=0.018）。相比之下，CM 基序模式与组织学评分和临床结局之间没有显著关联。
我们在西方型 CagA 中发现了独特的非洲 CM 基序，并将其命名为 Africa1-CM。这种基序的毒性较低可能是解释非洲之谜的一个原因。
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