Genetic Polymorphism And MRNA Ievels Of CYP1A1 And PPARα In Alcoholic Liver Disease

Background and Aim:The epidemiological survey of alcoholic liver disease (ALD) showed that ALD is associated with the genetics. This study analyzes genetic polymorphism of cytochrome P4501A1 (CYP1A1) and peroxisome proliferator-activated receptor-a(PPARa) in ALD patients of three nationalities.METHODS:Peripheral blood were collected in 464 patients with ALD,450 alcohol dependent patients without liver disease (alcoholic), and 480 healthy controls. Then PCR-RFLP was used to each group including patients from the Han, Mongol and Korean nationalities. Real-time polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP) were used to analyze genetic polymorphism and mRNA of CYP1A1 and PPARa. Age, sex, duration of drinking, Serumγ-glutamyltransferase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and total bilirubin (TB) were assessed.RESULTS:The frequency of CYPIA1 m2 and PPARa 227Ala alleles in patients with ALD were 20.43% and 3.7% in Han nationality patients,20.95% and 3.4% in the Mongol group, and 20.13% and 3.9% in the Korean group In contrast, the corresponding frequencies in the alcoholic patients were 7.33% and 10% in the Han patients,5.33% and 10.7% in the Mongol group, and 6.67% and 10% in the Korean group, the corresponding frequencies in the control patients were 10% and 9.4% in the Han patients,9.38% and 10% in the Mongol group, and 8.75% and 10.6% in the Korean group. The average mRNA levels of CYP1A1 in ALD patients and healthy controls were 20.34% and 9.73% respectively. The average mRNA levels of GSTP1 in ALD patients and healthy controls were 11.26% and 24.93% respectively. The polymorphism of CYP1A1 and PPARa has no difference in three nationalities. Serum AST, GGT and TB levels in carriers of the m2 allele with ALD patients were significantly higher than those in non-carriers (P<0.05). These data revealed an increased frequency of the m2 and a decreased 227Ala alleles genotype in ALD patients as compared to either controls or alcoholics. The CYP1A1 expression is higher but the PPARa expression is lower in ALD patients than the controls.CONCLUSION:The genetic polymorphism of CYP1A1 and PPARa on the position of m2 and 227Ala is related to the susceptibility of ALD. Besides, m2 gene may play a role in the pathogenetic condition of ALD. The higher expression of the CYP1A1 and the lower expression of PPARa reveals a causal relationship to the development of ALD.