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酒精代谢酶的遗传多态性与波兰男性的酒精依赖。

Genetic polymorphism of alcohol-metabolizing enzyme and alcohol dependence in Polish men.

机构信息

Department of Gastroenterology, Medical University of Lublin, Poland.

出版信息

Braz J Med Biol Res. 2010 Mar;43(3):257-61. doi: 10.1590/s0100-879x2010007500006.

Abstract

Alcohol dependence poses a serious medical and sociological problem. It is influenced by multiple environmental and genetic factors, which may determine differences in alcohol metabolism. Genetic polymorphism of the enzymes involved in alcohol metabolism is highly ethnically and race dependent. The purpose of this study was to investigate the differences, if present, in the allele and genotype frequency of alcohol dehydrogenase 1B (ADH1B), ADH1C and the microsomal ethanol-oxidizing system (MEOS/CYP2E1) between alcohol-dependent individuals and controls and also to determine if these genotypes cause a difference in the age at which the patients become alcohol dependent. The allele and genotype frequencies of ADH1B, ADH1C, and CYP2E1 were determined in 204 alcohol dependent men and 172 healthy volunteers who do not drink alcohol (control group). Genotyping was performed by PCR-RFLP methods on white cell DNA. ADH1B1 (99.3%) and ADH1C1 (62.5%) alleles and ADH1B1/1 (N = 201) and ADH1C1/1 (N = 85) genotypes were statistically more frequent among alcohol-dependent subjects than among controls (99.3 and 62.5%, N = 201 and 85 vs 94.5 and 40.7%, N = 153 and 32, respectively). Differences in the CYP2E1 allele and genotype distribution between groups were not significant. The persons with ADH1C1/1 and CYP2E1c1/c2 genotypes became alcohol dependent at a considerably younger age than the subjects with ADH1C1/2, ADH1C2/2 and CYP2E1c1/c1 genotypes (28.08, 25.67 years vs 36.0, 45.05, 34.45 years, respectively). In the Polish men examined, ADH1C1 and ADH1B1 alleles and ADH1C1/1 and ADH1B1/1 genotypes favor alcohol dependence. The ADH1B2 allele may protect from alcohol dependence. However, subjects with ADH1C1/1 and CYP2E1c1/c2 genotypes become alcohol dependent at a considerably younger age than the subjects with ADH1C1/2, ADH1C2/2 and CYP2E1c1/*c1 genotypes.

摘要

酒精依赖是一个严重的医学和社会学问题。它受到多种环境和遗传因素的影响,这些因素可能决定了酒精代谢的差异。参与酒精代谢的酶的遗传多态性高度依赖于种族和民族。本研究的目的是探讨酒精依赖患者与对照组之间,醇脱氢酶 1B(ADH1B)、ADH1C 和微粒体乙醇氧化系统(MEOS/CYP2E1)等位基因和基因型频率是否存在差异,以及这些基因型是否导致患者出现酒精依赖的年龄差异。在 204 名酒精依赖男性和 172 名不饮酒的健康志愿者(对照组)的白细胞 DNA 中,测定了 ADH1B、ADH1C 和 CYP2E1 的等位基因和基因型频率。通过 PCR-RFLP 方法进行基因分型。ADH1B1(99.3%)和 ADH1C1(62.5%)等位基因和 ADH1B1/1(N=201)和 ADH1C1/1(N=85)基因型在酒精依赖患者中比对照组更为常见(99.3%和 62.5%,N=201 和 85 与 94.5%和 40.7%,N=153 和 32,分别)。两组间 CYP2E1 等位基因和基因型分布的差异无显著性。具有 ADH1C1/1 和 CYP2E1c1/c2 基因型的人比具有 ADH1C1/2、ADH1C2/2 和 CYP2E1c1/c1 基因型的人更早出现酒精依赖(分别为 28.08、25.67 岁和 36.0、45.05、34.45 岁)。在被检查的波兰男性中,ADH1C1 和 ADH1B1 等位基因以及 ADH1C1/1 和 ADH1B1/1 基因型有利于酒精依赖。ADH1B2 等位基因可能具有保护作用,防止酒精依赖。然而,具有 ADH1C1/1 和 CYP2E1c1/c2 基因型的人比具有 ADH1C1/2、ADH1C2/2 和 CYP2E1c1/*c1 基因型的人更早出现酒精依赖。

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