| Project/Area Number |
16590613
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Fukui Prefectural University |
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Principal Investigator |
KATO Takuji Fukui Prefectural University, Faculty of Nursing and Welfare, Professor, 看護福祉学部, 教授 (70145902)
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| Co-Investigator(Kenkyū-buntansha) |
AZUMA Takeshi Kobe University, Professor, 医学部, 教授 (60221040)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2004: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Keywords | H.pylori / CagA / Gastric cancer / H.pylori / VacA |
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| Research Abstract |
Helicobacter pylori (H.pylori) is a human pathogen responsible for chronic active gastritis, and infection with this organism is an important risk factor for gastric cancer. The severity of H.pylori-related disease is correlated with the presence of a cag pathogenicity island (PAI). Genetic diversity within the cag PAI may have a modifying effect on the pathogenic potential of the infecting strain. We analyzed complete cag PAI sequences of 11 representative Japanese strains, and examined the relationship between the diversity of cag PAI and clinical features. The cag PAI genes were divided into two major groups, a Western and a East Asian group, by phylogenetic analysis based on the entire cag PAI sequences. Our molecular analysis has provided the pathological actions of CagA (cagA gene is located in cag PAI) on gastric epithelial cells. CagA is injected into epithelial cells via the type IV secretion system and undergoes tyrosine phosphorylation in the cells. In addition, translocated CagA forms a physical complex with SHP-2. There are two major CagA subtypes ; the East Asian and the Western type. The East Asian CagA protein possesses stronger SHP-2 binding activity than the Western CagA. The grades of inflammation, activity of gastritis, and atrophy are significantly higher in gastritis patients infected with the East Asian CagA-positive strain than in gastritis patients infected with the cagA-negative or Western CagA-positive strains. The prevalence of the East Asian CagA-positive strain is associated with the mortality rate of gastric cancer in Asia. Endemic circulation of H.pylori populations carrying biologically more active CagA proteins in East Asian countries, where the mortality rate of gastric cancer is among the highest in the world, may be involved in increasing the risk of gastric cancer in these populations.
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