Clinical relevance of the Helicobacter pylori gene for blood-group antigen-binding adhesin
Clinical relevance of the Helicobacter pylori gene for blood-group antigen-binding adhesin
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DOI：
10.1073/pnas.96.22.12778
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发表时间：
1999-10-26
影响因子：
11.1
通讯作者：
Prinz, C
中科院分区：
文献类型：
--
作者：
Gerhard, M;Lehn, N;Prinz, C
幽门螺杆菌感染与不同的人类胃部疾病有关。生化研究、体外粘附实验和体内动物模型显示，针对人类Lewis(b)表面表位的血型抗原结合粘附素（BabA）可以介导幽门螺杆菌的上皮附着。对表达Lewis(b)表位的转基因小鼠的研究表明，这种附着可以改变疾病结局。在本研究中，我们利用PCR和逆转录-PCR技术研究了德国人群临床分离株中编码粘附素的babA2基因的存在。阳性基因型与编码VacA和CagA基因的等位基因变异相关，也与十二指肠溃疡、胃远端腺癌、粘膜相关淋巴组织淋巴瘤和胃窦性炎的患病率相关。babA2的存在与十二指肠溃疡（P = 0.0002）和腺癌（P = 0.033）显著相关。相比之下，1型菌株（vacAs1-和caga阳性）仅与十二指肠溃疡相关（P = 0.004），而与腺癌无关（P = 0.235）。babA2、vacAs1和cagA（“三阳性”菌株）的基因型存在与溃疡（P = 0.000002）和腺癌（P = 0.014）的患病率高度显著相关，并且与目前的1型分类相比，在疾病结局之间有明显更好的区分。这些结果表明babA2基因具有很高的临床相关性，并将成为识别特定幽门螺杆菌相关疾病高风险患者的有用标记。
Infection with Helicobacter pylori is associated with different human gastric diseases. Biochemical studies, in vitro adherence assays, and in vivo animal models revealed that epithelial attachment of H. pylori can be mediated by the blood-group antigen-binding adhesin (BabA) targeting human Lewis(b) surface epitopes, Studies with transgenic mice expressing the Lewis(b) epitope have shown that such attachment can alter disease outcome. In the current study, the presence of the babA2 gene encoding the adhesin was investigated in clinical isolates from a German population by using PCR and reverse transcription-PCR. A positive genotype was correlated to allelic variations in the genes encoding VacA and CagA and also to the prevalence of duodenal ulcer, distal gastric: adenocarcinoma, mucosa-associated lymphoid tissue lymphoma, and antral gastritis. The presence of babA2 was significantly associated with duodenal ulcer (P = 0.0002) and adenocarcinoma (P = 0.033). In contrast, type 1 strains (vacAs1- and cagA-positive) were associated with only duodenal ulcer (P = 0.004) but not adenocarcinoma (P = 0.235). Genotype presence of babA2, vacAs1, and cagA ("triple-positive" strains) showed a highly significant correlation to the prevalence of ulcer (P = 0.000002) and adenocarcinoma (P = 0.014) and discriminated significantly better between disease outcome than did the current type 1 classification. These results indicate that the babA2 gene is of high clinical relevance and would he a useful marker to identify patients who are at higher risk for specific H. pylori-related diseases.