Clinical and pathological importance of heterogeneity in vacA, the vacuolating cytotoxin gene of Helicobacter pylori
Clinical and pathological importance of heterogeneity in vacA, the vacuolating cytotoxin gene of Helicobacter pylori
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DOI：
10.1016/s0016-5085(97)70223-3
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发表时间：
1997-01-01
期刊：
影响因子：
29.4
通讯作者：
Blaser, MJ
中科院分区：
文献类型：
--
作者：
Atherton, JC;Peek, RM;Blaser, MJ
背景与目的：vacA编码幽门螺杆菌的空泡细胞毒素，在信号序列和中间基因编码区表现出明显的差异，对胃十二指肠病理的影响尚不清楚，本研究的目的是确定vacA基因型与胃炎症和损伤、体外细胞毒素活性和消化性溃疡的关系。连续61例消化不良患者行胃镜检查和胃活检，活检标本行幽门螺杆菌培养，52例标本行组织学检查，采用聚合酶链反应和集落杂交分型幽门螺杆菌vacA。通过HeLa细胞空泡实验评估细胞毒素活性。结果：vacA信号序列型sla菌株与s1b、s2菌株相比，胃窦粘膜中性粒细胞和淋巴细胞浸润明显增加（P < 0.05）。在体外实验中，vvaca中间区型mi菌株的胃上皮损伤程度高于m2菌株（P < 0.05），中间区和信号序列均与细胞毒素活性相关，18例s1a菌株中89% （P < 0.01）、14例s1b菌株中29% （P < 0.01）、10例s2菌株中20% （P < 0.001）、19例未感染患者中16% （P < 0.001）发生十二指肠溃疡。结论：幽门螺杆菌vacA信号序列型sla与胃炎症和十二指肠溃疡加重有关。vacA s2菌株与较少的炎症和较低的溃疡患病率相关。
Background & Aims: vacA encodes the vacuolating cytotoxin of Helicobacter pylori and exhibits marked variation in signal sequence and midgene coding regions, The implications for gastroduodenal pathology are unknown, The aim of this study was to define the association of vacA genotype with gastric inflammation and injury, in vitro cytotoxin activity, and peptic ulceration, Methods: Sixty-one consecutive dyspeptic patients underwent endoscopy and gastric biopsy, The biopsy specimens were processed for H. pylori culture, and 52 specimens were also processed for histology, H. pylori vacA was typed by polymerase chain reaction and colony hybridization. Cytotoxin activity was assessed by a HeLa cell vacuolation assay. Results: vacA signal sequence type sla strains were associated with greater antral mucosal neutrophil and lymphocyte infiltration than s1b or s2 strains (P < 0.05). vacA midregion type mi strains were associated with greater gastric epithelial damage than m2 strains (P < 0.05), Both midregion and signal sequence were associated with cytotoxin activity in vitro, Duodenal ulcer disease occurred in 89% of 18 patients with s1a strains vs. 29% of 14 with s1b strains (P < 0.01), 20% of 10 with s2 strains (P < 0.001), and 16% of 19 uninfected patients (P < 0.001). Conclusions: H. pylori strains of vacA signal sequence type sla are associated with enhanced gastric inflammation and duodenal ulceration. vacA s2 strains are associated with less inflammation and lower ulcer prevalence.