Satomi Satoko, Yamakawa Akiyo, Matsunaga Shinsuke, Masaki Ryuho, Inagaki Tomoko, Okuda Tomoyuki, Suto Hiroyuki, Ito Yoshiyuki, Yamazaki Yukinao, Kuriyama Masaru, Keida Yoshihide, Kutsumi Hiromu, Azuma Takeshi
Second Department of Internal Medicine, Faculty of Medical Science, University of Fukui, Fukui, Japan.
J Gastroenterol. 2006 Jul;41(7):668-73. doi: 10.1007/s00535-006-1838-6.
Helicobacter pylori CagA protein is considered to be one of the virulence factors associated with gastric cancer. CagA is injected into gastric epithelial cells, undergoes tyrosine phosphorylation, and binds to Src homology 2 domain-containing protein-tyrosine phosphatase (SHP-2). Two major subtypes of CagA have been observed in the SHP-2-binding site, the Western and East Asian types. The East Asian-type CagA binds to SHP-2 more strongly than the Western-type CagA. The diversity of CagA, which collectively determines the binding affinity of CagA to SHP-2, may be an important variable in determining the clinical outcome of infection by different H. pylori strains.
We investigated the relationship between the diversity of CagA and clinical outcome in Okinawa, Japan. A total 24 strains, 13 gastric cancer strains and 11 duodenal ulcer strains, were studied. We sequenced full-length cagA genes and analyzed the phylogenetic relationships between Okinawa isolates and previously characterized Western H. pylori strains.
All isolates examined were cagA positive. The prevalence of East Asian CagA-positive strains was significantly higher in patients with gastric cancer (84.6%) than in patients with duodenal ulcer (27.3%) (chi-squared = 8.06, P = 0.011). The phylogenetic analysis showed that all gastric cancer strains with East Asian-type CagA were in the East Asian cluster, and that most duodenal ulcer strains were in the Western cluster.
The origins of H. pylori isolates are different between gastric cancer strains and duodenal ulcer strains, and East Asian CagA-positive H. pylori infection is associated with gastric cancer. The strain diversity observed in Okinawa may affect the difference in the prevalence of disease associated with H. pylori infection in Japan.
幽门螺杆菌细胞毒素相关基因A（CagA）蛋白被认为是与胃癌相关的毒力因子之一。CagA被注入胃上皮细胞，发生酪氨酸磷酸化，并与含Src同源2结构域的蛋白酪氨酸磷酸酶（SHP-2）结合。在SHP-2结合位点观察到CagA的两种主要亚型，即西方型和东亚型。东亚型CagA比西方型CagA与SHP-2的结合更强。CagA的多样性共同决定了CagA与SHP-2的结合亲和力，可能是决定不同幽门螺杆菌菌株感染临床结果的一个重要变量。
我们在日本冲绳研究了CagA多样性与临床结果之间的关系。共研究了24株菌株，其中13株胃癌菌株和11株十二指肠溃疡菌株。我们对全长cagA基因进行了测序，并分析了冲绳分离株与先前鉴定的西方幽门螺杆菌菌株之间的系统发育关系。
所有检测的分离株cagA均为阳性。东亚型CagA阳性菌株在胃癌患者中的患病率（84.6%）显著高于十二指肠溃疡患者（27.3%）（卡方检验=8.06，P=0.011）。系统发育分析表明，所有具有东亚型CagA的胃癌菌株都在东亚簇中，而大多数十二指肠溃疡菌株在西方簇中。
胃癌菌株和十二指肠溃疡菌株中幽门螺杆菌分离株的来源不同，东亚型CagA阳性幽门螺杆菌感染与胃癌相关。在冲绳观察到的菌株多样性可能影响日本与幽门螺杆菌感染相关疾病患病率的差异。
