Genetic factors of alcoholic liver disease and polymorphisms of cytochrome P4502E1.

应用限制性片段长度多态性技术测定酒精性肝病（ALD）患者细胞色素P4502E1 （P4502E1）基因型。P4502E1放大的DNA片段聚合酶链反应是处理两种类型的内切酶,Rsa我和Pst的c1基因I P4502E1与Rsa我消化,但不是Pst我,和c2基因与Pst我消化,但不是与Rsa。因此,P4502E1的基因型是分为3种类型:类型为c1基因纯合,B型这是杂合的c1和c2基因和C为c2基因纯合类型。在31例ALD患者中，29例（93.5%）被检测为P4502E1的B型基因型，2例（6.3%）被检测为c型基因型。另一方面，所有没有ALD的重度饮酒者都有A型糖尿病。在健康对照组中，A型占63.3%。ALD患者与健康对照者或无ALD的重度饮酒者的基因型患病率差异有统计学意义。这些结果表明ALD的发生受遗传控制，P4502E1基因型是其发生的最重要的决定因素。B型的肝脏信使RNA含量比a型高3倍。这些结果也表明，即使在人肝脏中，c2基因的转录活性也比c1基因强。这些结果表明，P4502E1基因的多态性可能通过增强非酒精脱氢酶途径中的乙醇代谢与ALD的发生有关。

Genotypes of cytochrome P4502E1 (P4502E1) were determined by the restriction fragment length polymorphisms technique in patients with alcoholic liver disease (ALD). DNA fragments of P4502E1 amplified by polymerase chain reactions were treated with 2 types of endonucleases, Rsa I and Pst I. The c1 gene of P4502E1 was digested with Rsa I, but not with Pst I, and the c2 gene was digested with Pst I, but not with Rsa I. Consequently, the genotypes of P4502E1 were separated into 3 types: type A which is homozygous for the c1 gene, type B which is heterozygous for the c1 and c2 genes and type C which is homozygous for the c2 gene.In 31 patients with ALD, 29 (93.5%) were determined to have the type B genotype of P4502E1 and 2 (6.3%) the type C. Type A was not found in any patient with ALD. On the other hand, type A was found in all of the heavy drinkers without ALD. In healthy controls, type A was found in 63.3%. The difference in prevalence of genotypes between patients with ALD and healthy controls or heavy drinkers without ALD was significant statistically. These results indicate that the development of ALD is controlled genetically and that the genotype of P4502E1 is the most important determining factor in its development. Hepatic messenger RNA contents in type B were 3 times higher than in type A. These results also indicate that the transcriptional activity of the c2 gene is stronger than that of the c1 gene, even in human livers. These results lead to the conclusion that polymorphisms of the P4502E1 gene may be linked to development of ALD through enhancement of ethanol metabolism in the non-alcohol dehydrogenase pathway.