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

(1)建立了一种准确、简便的乙醇脱氢酶2(ADH2)和乙醛脱氢酶2(ALDH2)基因分型方法。(2)对WHO(AUDIT)建立的酒精障碍鉴定试验(AUDIT)进行了修改并翻译成日语(K/AUDIT)，适用于日本九州北部地区。基于精神病学专家确认的106例酒精使用障碍(AUD)患者和其他疾病的非AUD患者，检验了K/AUDIT的标准相关效度。(3)应用聚合酶链式反应-单链构象多态性分析(κ-SSCP)方法对106对AUD-非AUD患者进行了病例对照研究，发现ADH2^；/1&gt；或ALDH2^；/1&gt；(4)在福冈县和佐贺县进行的一项关于原发性肝细胞癌的病例对照研究产生了177例男性肝癌病例，以及年龄、性别、居住地相匹配的医院对照。数据，如乙肝表面抗原、抗-HCVAb、生活方式信息，如吸烟或饮酒，都是通过对指甲皱痕的结构化访谈收集的。Logistic回归模型单因素分析显示，乙肝表面抗原阳性、抗-HCVAb阳性、大量饮酒(40岁前平均饮酒年限为60年以上)和ALDH2；/1&gt；纯合子分别是男性肝癌发生的危险因素。

(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.