Genetic polymorphism and mRNA levels of cytochrome P450ⅡE1 and glutathione S-transferase P1 in patients with alcoholic liver disease in different nationalities

摘要

BACKGROUND: Alcohol abuse and dependence are major factors in the pathogenesis of alcoholic liver disease (ALD). Alcohol abuse is becoming an increasingly severe problem among the Han, Mongol, and Korean nationalities in northeast China. This study aimed to investigate the relationship between ALD and the genetic polymorphism and expression levels of two enzymes, cytochrome P450ⅡE1 (CYPⅡE1) and glutathione S-transferase P1 (GSTP1) in patients of three nationalities. METHODS: Peripheral blood was collected from 353 Chinese patients with ALD, 300 alcohol dependent patients without liver disease (alcoholic), and 360 healthy controls. Each group included patients from the Han, Mongol and Korean nationalities. Real-time polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP) were used. RESULTS: Regardless of nationality, patients who carried the rare CYPⅡE1 C2 and GSTP1 Val alleles were at higher risk of ALD. The frequency of C2 and Val in patients with ALD was respectively 50.00% and 26.98% in the Han, 31.36% and 22.87% in the Mongol, and 45.87% and 22.02%in theKorean nationality. No signiifcant differences were seen in the frequency of either C2 or Val alleles in ALD patients among the three nationalities. In each nationality, the frequencyof both C2 and Val alleles was signiifcantly higher in ALD compared to alcoholic and healthy controls. Except for nationality, the average mRNA levels of CYPⅡE1 in ALD patients and healthy controls were 10.05% and 2.21%, respectively. The average mRNA levels of GSTP1 in ALD patients and healthy controls were 0.53% and 2.12%, respectively. The mRNA level of CYPⅡE1 was higher, and that of GSTP1 was lower in patients with ALD compared to the controls. CONCLUSIONS: Except for nationality, patients with ALD in this series tended to have a higher mRNA expression of CYPⅡE1 and to carry the C2 allele, and tended to have a lower mRNA expression of GSTP1 and to carry the Val allele. There is a causal relationship between the polymorphic alleles, which leads to different mRNA levels and the development of ALD.