Gene expression and gene polymorphisms related with chole-pancreatic diseases

胆胰疾病相关基因表达及基因多态性

• 批准号: 15390237
• 负责人: MIYASAKA Kyoko
• 金额: $ 9.47万
• 依托单位: Tokyo Metropolitan Foundation of Research on Aging and Promotion of Human Welfare
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-15390237/
• 关键词: 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

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.

我们发现基因多态性与胆胰疾病呈正相关。CCK-A受体（AR）基因多态性（-81A/G, -128G1T）与惊恐障碍、酒精中毒和肥胖有关。肾上腺素- 3R突变（Trp64Arg）与较高的BMI有关，而ALDH2突变（Glu to Lys）与吸烟者患胰腺癌的风险有关。生长素受体多态性（177T/C）是神经性贪食症的危险因素。CEL基因多态性与酒精性胰腺炎相关。SHIP2基因多态性与葡萄糖耐受不良有关。然而，我们没有发现西方国家报道的PAR2、Klotho、Cyp2A6和Ghrelin的多态性。胆囊结石患者胆囊CCK-AR基因表达降低。然而，CCK-AR多态性与CCK-AR基因表达水平是否存在正相关尚不清楚。我们观察到CCK-ARKO小鼠的新表型。CCK-ARKO小鼠在抑制应激后表现出暴饮暴食的现象，并且比其他基因型小鼠饮酒更多，这可能与伏隔核中多巴胺2R蛋白的表达较高有关。与野生型小鼠相比，CCK ARKO小鼠胆石形成频率增加，但性别差异尚不清楚。

项目成果

Lack of cholecystokinin (CCK)-A receptor enhanced gallstone formation: A study in CCK-A receptor gene knockout mice.

胆囊收缩素 (CCK)-A 受体缺乏会增强胆结石形成：CCK-A 受体基因敲除小鼠的一项研究。

• 发表时间: 2003
• 期刊: Dig Dis Sci 48
• 作者: Sato N;Miyasaka K;Suzuki S;Kanai S;Ohta M;Kawanami T;Yoshida Y;Takiguchi S;Noda T;Takata Y;Funakoshi A.
• 通讯作者: Funakoshi A.

Carboxylester lipase gene polymorphism as a risk of alcohol-induced pancreatitis

• DOI: 10.1097/01.mpa.0000160960.21580.ml
• 发表时间: 2005-05-01
• 期刊: PANCREAS
• 影响因子: 2.9
• 作者: Miyasaka, K;Ohta, M;Funakoshi, A
• 通讯作者: Funakoshi, A

Physiological and pathological age-associated changes in diurnal rhythm of energy expenditure in rats.

大鼠能量消耗昼夜节律的生理和病理年龄相关变化。

• 发表时间: 2004
• 期刊: Arch Geriat Gerontol 39
• 作者: Miyasaka K;Ichikawa M;Momose K;Araki A;Kobayashi M;Ichimaru Y;Funakoshi A.
• 通讯作者: Funakoshi A.

Absence of the cholecystokinin-A receptor deteriorates homeostasis of body temperature in response to changes in ambient temperature.

胆囊收缩素-A 受体的缺失会导致体温响应环境温度变化的稳态恶化。

• 发表时间: 2004
• 期刊: Am J physiol : Regul Integrative 287
• 作者: Nomoto S;Ohta M;Kanai S;Yoshida Y;Takiguchi S;Funakoshi A;Miyasaka K.
• 通讯作者: Miyasaka K.

Sp-family of transcription factors regulates the human SHIP2 gene expression

转录因子 Sp 家族调节人类 SHIP2 基因表达

• 发表时间: 2005
• 期刊: Gene 348
• 作者: Ishida S;et al.;Miyasaka K;et al.
• 通讯作者: et al.