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Molecular epidemiological study on relationship between alcohol metabolizing Enzyme and alcohol-related diseases

酒精代谢酶与酒精相关疾病关系的分子流行病学研究

基本信息

批准号：
09470105
负责人：
FUKUDA Katsuhiro
金额：
$ 2.5万
依托单位：
Kurume University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B).
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 2000
项目状态：
已结题

项目摘要

(1) An accurate and easy genotyping method of alcohol dehydrogenase2 (ADH2) and aldehyde dehydrogenase2 (ALDH2) by PCR-SSCP has been developped using nail clippings.(2) The alcohol disorder identification test developed by WHO (AUDIT) has been modified and translated into Japanse (K/AUDIT) which can be applicable for use in the northern Kyushu area in Japan. Based on psychiatry-specialist-confirmed 106 alcohol use disorder (AUD) patients and non-AUD patients with other diseases, the K/AUDIT's criterion-related-validity has been examined. Applying score 12 as the cut-off score to them, the proportion of correct screening of AUD was 0.939, with κ statistics, sensitivity and specificity being 0.877, 0.915 and 0.962, respectively.(3) Applying the PCR-SSCP method for ADH2 and ALDH2 genotyping, a case-control study on 106 AUD-non-AUD pairs was performed and revealed that a person with ADH2^</1> or a person with ALDH2^</1> showed 3.5 (P<0.05) or 7.1 (P<0.05) times likely to develop AUD than those with other genotypes, respectively.(4) A case-control study performed on primary hepatocellular carcinoma (HCC) in Fukuoka and Saga Prefecture produced 177 male HCC cases, and age-, sex-, residence-matched hospital-based controls. Data e.g. HBsAg, anti-HCVAb, life-style infomations e.g. smoking or drinking havits have been collectd by a structured interview with nail crippings. Univariate analysis using logistic regression model revealed that factors ; HbsAg positive, anti-HCVAb positive, heavy drinking (average drinking amount by age 40 was 60 drink-years or more) and ALDH2^</1> homozygote were statistically significant risk factors for developing male HCC, respectively.

(1)建立了一种准确、简便的指甲油中乙醇脱氢酶2（ADH 2）和乙醛脱氢酶2（ALDH 2）的PCR-SSCP分型方法。(2)世界卫生组织（WHO）开发的酒精障碍鉴别试验（AUDIT）已被修改并翻译成日语（K/AUDIT），可适用于日本北方九州地区。以106例经精神科专家确诊的酒精使用障碍（AUD）患者和非AUD患者为研究对象，对K/AUDIT的效标相关效度进行了检验。以12分为分界分，AUD的正确筛查比例为0.939，κ统计量、敏感性和特异性分别为0.877、0.915和0.962。(3)应用PCR-SSCP方法对106对AUD与非AUD配对进行了ADH 2和ALDH 2基因分型的病例对照研究，发现ADH 2 ^</1>和ALDH 2 ^</1>基因型者发生AUD的可能性分别是其他基因型者的3.5倍（P<0.05）和7.1倍（P<0.05）。(4)一项在福冈和佐贺县进行的原发性肝细胞癌（HCC）病例对照研究产生了177例男性HCC病例，以及年龄、性别、居住地匹配的基于医院的对照。采用指甲刮片结构化访谈法收集HBsAg、抗-HCV抗体、吸烟、饮酒等生活方式资料。单因素Logistic回归分析显示，HBsAg阳性、抗-HCVAb阳性、大量饮酒（40岁时平均饮酒量为60饮酒年或以上）和ALDH 2 β</1>纯合子分别为男性肝癌的显著危险因素。