Effect of genetic polymorphism of the cytochrome P-450 and glutathione-S-transferase families on the severity of toxic hepatitis in acute poisoning and endotoxicosis

Abstract

Material and methods. The results of a survey of 138 patients with acute poisoning with hepatotoxic poisons (alcohol intoxication, poisoning with acetic acid, paracetamol), as well as patients with severe thermal burns, were studied. The polymorphism of the genes – rs1965 of the
GSTP1 gene and rs2070676 of the CYP2E1 gene was studied in all the above patients. Data from
genetic studies were compared with biochemical parameters of liver damage at admission.
Results. The results of the study of the GSTP1 gene (rs1965) showed that the A/A genotype (homozygous for allele A) was detected in 45 (32.6%) patients, the A/G genotype (heterozygote) was detected in 68 (49.2%) patients, the genotype G/G (homozygous for the G
allele) was detected in 25 (18.1%) patients. The results of the study of the CYP2E1 gene
(rs2070676) showed that the C/C genotype (homozygous for allele A) was detected in 86
(62.3%) patients, the G/C genotype (heterozygous) was detected in 32 (23.1%) patients, genotype G/G (homozygous for allele G) was detected in 20 (14.4%) patients. In patients with
the G/G genotype (homozygous for the G allele) of the GSTP1 and CYP2E1 genes, we observed a significant increase in free ammonia, as well as in the liver parameters of ALT, AST, not
only in comparison with the norm, but also in those of patients with a homozygous type for
alleles A and C Analysis of mortality showed a significant increase in mortality in patients
with the G/G genotype of the GSTP1 or CYP2E1 genes. In 9 patients, a mutation in both genes
was detected, while their biochemical parameters and lethality were more than twice as high
as in patients with mutations in only one of the studied genes.
Conclusions. The nature of the course of toxic hepatitis is largely determined by the genetic
component. The most severe course of toxic hepatitis was found against the background of
polymorphism in both studied genes.