西班牙男性中乙醇脱氢酶2、乙醇脱氢酶3、细胞色素P450 2E1 Dra-I和Pst-I以及乙醛脱氢酶2的基因多态性：与酒精中毒和酒精性肝病无关联

Genetic polymorphisms of ADH2, ADH3, CYP4502E1 Dra-I and Pst-I, and ALDH2 in Spanish men: lack of association with alcoholism and alcoholic liver disease.

作者信息

Vidal Francesc, Lorenzo Alfons, Auguet Teresa, Olona Montserrat, Broch Montserrat, Gutiérrez Cristina, Aguilar Carmen, Estupiñà Pere, Santos Mauro, Richart Cristóbal

机构信息

Department of Internal Medicine, Hospital Universitari de Tarragona Joan XXIII, C/Dr. Mallafré Guasch, 4, 43007 Tarragona, Spain.

出版信息

J Hepatol. 2004 Nov;41(5):744-50. doi: 10.1016/j.jhep.2003.06.003.

DOI:10.1016/j.jhep.2003.06.003

PMID:15519646

Abstract

BACKGROUND/AIMS: The relationship between polymorphisms at the alcohol dehydrogenase 2 (ADH(2)), ADH(3), CYP(450)2E1 and aldehyde dehydrogenase 2 (ALDH(2)) loci and the individual predisposition to alcoholism and alcoholic liver disease in Caucasians is controversial.

METHODS

We determined the genotypes of ADH(2), ADH(3), CYP(450)2E1 (Pst-I and Dra-I) and ALDH(2) in 519 male Spaniards: 264 alcoholic subjects (47 without liver disease, 118 with non-cirrhotic liver disease and 99 with cirrhosis) and 255 non-alcoholic subjects (64 healthy controls, 110 with non-cirrhotic non-alcoholic liver disease and 81 with cirrhosis unrelated to alcohol). Genotyping was performed using PCR-RFLP methods on white cell DNA.

RESULTS

The distribution of the allelic variants (allele *1 and allele *2) in the whole subjects analyzed was: ADH(2) 93.1% and 6.9%; ADH(3) 55.7 and 44.3%; CYP(450)2E1 Dra-I 11.2 and 88.8%; CYP(450)2E1 Pst-I 96.2 and 3.8% and ALDH2 100 and 0%, respectively. No differences were observed in the allelic distributions of the alcoholic and non-alcoholic subjects for the loci examined. Allele distribution in alcoholics with no liver disease, with alcoholic steatosis or hepatitis, and with cirrhosis was also similar.

CONCLUSIONS

ADH(2), ADH(3), and CYP(450)2E1 Pst-I and Dra-I genetic variations are not related to alcoholism or susceptibility to alcoholic liver disease in our male population. ALDH(2) locus is monomorphic.

摘要

背景/目的：乙醇脱氢酶2（ADH(2)）、ADH(3)、细胞色素P450 2E1（CYP(450)2E1）和乙醛脱氢酶2（ALDH(2)）基因座的多态性与白种人个体对酒精中毒和酒精性肝病的易感性之间的关系存在争议。

方法

我们测定了519名西班牙男性中ADH(2)、ADH(3)、CYP(450)2E1（Pst-I和Dra-I）和ALDH(2)的基因型：264名酒精中毒者（47名无肝病，118名患有非肝硬化性肝病，99名患有肝硬化）和255名非酒精中毒者（64名健康对照，110名患有非肝硬化性非酒精性肝病，81名患有与酒精无关的肝硬化）。使用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法对白细胞DNA进行基因分型。

结果

在分析的所有受试者中，等位基因变异（等位基因1和等位基因2）的分布分别为：ADH(2) 93.1%和6.9%；ADH(3) 55.7%和44.3%；CYP(450)2E1 Dra-I 11.2%和88.8%；CYP(450)2E1 Pst-I 96.2%和3.8%；以及ALDH2 100%和0%。在所检测的基因座中，酒精中毒者和非酒精中毒者的等位基因分布没有差异。无肝病、患有酒精性脂肪变性或肝炎以及患有肝硬化的酒精中毒者的等位基因分布也相似。