Polymorphisms in the Intermediate Region of VacA Impact Helicobacter pylori-Induced Disease Development
Polymorphisms in the Intermediate Region of VacA Impact Helicobacter pylori-Induced Disease Development
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DOI：
10.1128/jcm.01782-10
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发表时间：
2011-01-01
影响因子：
9.4
通讯作者：
Cha, Jeong-Heon
中科院分区：
文献类型：
--
作者：
Jones, Kathleen R.;Jang, Sungil;Cha, Jeong-Heon
幽门螺杆菌是胃炎、胃和十二指肠溃疡以及两种类型胃癌的病原体。虽然对这些不同表现的病因已经有了一些见解，但总的来说，一些人患上更严重疾病的原因仍然难以捉摸。最近的研究集中在幽门螺杆菌毒素CagA和VacA在疾病过程中的作用，并表明这两种毒素都有密切的关系。此外，CagA和VacA在不同的幽门螺杆菌菌株中是多态的，而且特定的多态似乎与特定疾病状态的发展相关。在VacA多态中，中间区域最近被认为在疾病转归中起主要作用。在这篇文章中，我们描述了从韩国大量人群中获得的菌株的VacA中间区多态序列的详细分析。我们发现，在第196位氨基酸发现的多态与更严重的疾病表现有关。此外，在氨基酸第231位发现的多态与携带非EPIYA-ABD等位基因CagA的菌株的疾病有关。总的来说，这些数据有助于解释VacA中间区对疾病的影响，并导致假设在VacA和CagA之间存在等位基因驱动的相互作用。
Helicobacter pylori is the etiological agent of diseases such as gastritis, gastric and duodenal ulcers, and two types of gastric cancers. While some insight has been gained into the etiology of these diverse manifestations, by and large, the reason that some individuals develop more severe disease remains elusive. Recent studies have focused on the roles of H. pylori toxins CagA and VacA on the disease process and have suggested that both toxins are intimately involved. Moreover, CagA and VacA are polymorphic within different H. pylori strains, and particular polymorphisms seem to show a correlation with the development of particular disease states. Among VacA polymorphisms, the intermediate region has recently been proposed to play a major role in disease outcome. In this article, we describe a detailed sequence analysis of the polymorphic intermediate region of vacA from strains obtained from a large South Korean population. We show that polymorphisms found at amino acid position 196 are associated with more severe disease manifestations. Additionally, polymorphisms found at amino acid position 231 are linked to disease in strains that carry the non-EPIYA-ABD allele of CagA. Collectively, these data help explain the impact of the VacA intermediate region on disease and lead to the hypothesis that there are allele-driven interactions between VacA and CagA.