CagA C-terminal variations in Helicobacter pylori strains from Colombian patients with gastric precancerous lesions.
CagA C-terminal variations in Helicobacter pylori strains from Colombian patients with gastric precancerous lesions.
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DOI：
10.1111/j.1469-0691.2009.02811.x
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发表时间：
2010-04
期刊：
影响因子：
--
通讯作者：
Schneider BG
中科院分区：
文献类型：
--
作者：
Sicinschi LA;Correa P;Peek RM;Camargo MC;Piazuelo MB;Romero-Gallo J;Hobbs SS;Krishna U;Delgado A;Mera R;Bravo LE;Schneider BG
幽门螺杆菌CagA蛋白的C末端是多态的，含有不同的EPIYA序列(EPIYA-A、B、C或D)，以及一个或多个CagA多聚化(CM)基序。EPIYA-C基序的数量与癌前病变和胃癌有关。在幽门螺杆菌感染的哥伦比亚患者中，研究了EPIYA、CM基序与胃粘膜病变的关系。从80例有消化不良症状的成人胃活检标本中提取幽门螺杆菌的基因组DNA。80株细菌中有67株(83.8%)cagA阳性。对cagA的3‘端序列进行了测序，并鉴定了EPIYA和CM基序。CagA蛋白含有1个(64.2%)、2个(34.3%)或3个EPIYA-C基序(1.5%)，均含有西式CagA特异性序列。具有一个EPIYA-C基序的菌株与较轻的胃病变(非萎缩性和多灶性萎缩性胃炎)相关，而具有多个EPIYA-C基序的菌株与较严重的病变(肠化生和异型增生)相关(p<；0.001)。在54个菌株中，CM基序与西方菌株中常见的相同。来自低风险地区的13株毒株含有两种不同的CM基序：一种位于EPIYA-C片段内的西式毒株，另一种位于EPIYA-C片段之后，与东亚毒株的CM基序相似。与具有Western/Western基序的菌株相比，这些菌株在免疫耗竭SHP-2时显著缩短了AGS细胞的投射，并减弱了CagA水平的降低。这一新发现可能部分解释了这些人群中GC发病率的差异。
The C-terminus of the Helicobacter pylori CagA protein is polymorphic, bearing different EPIYA sequences (EPIYA-A, B, C or D), and one or more CagA multimerization (CM) motifs. The number of EPIYA-C motifs is associated with precancerous lesions and gastric cancer (GC). The relationship between EPIYA, CM motifs and gastric lesions was examined in H. pylori-infected Colombian patients from areas of high and low risk for GC. Genomic DNA was extracted from H. pylori strains cultured from gastric biopsies from 80 adults with dyspeptic symptoms. Sixty-seven (83.8%) of 80 strains were cagA positive. The 3′ region of cagA was sequenced, and EPIYA and CM motifs were identified. CagA proteins contained one (64.2%), two (34.3%) or three EPIYA-C motifs (1.5%), all with Western type CagA-specific sequences. Strains with one EPIYA-C motif were associated with less severe gastric lesions (non-atrophic and multifocal atrophic gastritis), whereas strains with multiple EPIYA-C motifs were associated with more severe lesions (intestinal metaplasia and dysplasia) (p <0.001). In 54 strains, the CM motifs were identical to those common in Western strains. Thirteen strains from the low-risk area contained two different CM motifs: one of Western type located within the EPIYA-C segment and another following the EPIYA-C segment and resembling the CM motif found in East Asian strains. These strains induced significantly shorter projections in AGS cells and an attenuated reduction in levels of CagA upon immunodepletion of SHP-2 than strains possessing Western/Western motifs. This novel finding may partially explain the difference in GC incidence in these populations.
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影响因子：
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