| Project/Area Number |
15390237
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Tokyo Metropolitan Foundation of Research on Aging and Promotion of Human Welfare |
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Principal Investigator |
MIYASAKA Kyoko Tokyo Metro Found Res Aging and Promotion of Human Welfare, Tokyo Metro Inst Gerontology, 東京都老人総合研究所, 研究副部長 (90166140)
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| Co-Investigator(Kenkyū-buntansha) |
OHTA Minoru Tokyo Metro Found Res Aging and Promotion of Human Welfare, Tokyo Metro Inst Gerontology, Research Assistant, 東京都老人総合研究所, 助手 (70133634)
TAKIGUCHI Soichi Kyushu Cancer Center, Dept of Clinical Research, Researcher, 臨床研究部, 研究員 (00280793)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥14,800,000 (Direct Cost: ¥14,800,000)
Fiscal Year 2005: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2004: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 2003: ¥7,700,000 (Direct Cost: ¥7,700,000)
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| Keywords | SHIP2 / ALDH2 / gene polymorphism / pancreatic cancer / alcohol / 軽症糖尿病 / コレシストキニンA受容体 / 糖尿病 / SHIP-2 / 遺伝子ノックアウロマウス / 肥満 / 胆石 / インスリン |
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| Research Abstract |
We found positive associations of gene polymorphisms and chole-pancreatic disorders. The CCK-A receptor (AR) gene polymorphism (-81A/G, -128G1T) was associated with panic disorder, alcoholism, and obesity. The adrenalin beta 3R mutation (Trp64Arg) was associated with higher BMI, and ALDH2 mutation (Glu to Lys) was the risk of pancreatic cancer in the smokers. The ghrelin receptor polymorphism (177T/C) was a risk of Bulimia Nervosa. The CEL gene polymorphism was associated with alcoholic pancreatitis. The SHIP2 gene polymorphism was associated with glucose intolerance. However, we could not found polymorphisms of PAR2, Klotho, Cyp2A6, and Ghrelin, which had been reported in the Western counties.
The gene expression of CCK-AR was decreased in the gallbladder with gallstones. However, it is still unknown whether there were positive associations of CCK-AR polymorphism and the levels of CCK-AR gene expression.
We observed new phenotypes of CCK-ARKO mice. CCK-ARKO mice showed over-eating after the restraint stress, and they drank alcohol more than other genotypes, possibly due to the higher expression of dopamine 2R protein in the nucleus accumbens. The frequency of gallstone formation was increased in CCK ARKO mice, compared with wild-type mice, however, the sex difference was not clarified, yet.
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