Relationship of anti-tuberculosis drug-induced liver injury and genetic polymorphisms in CYP2E1 and GST.
SETTING
Treatment of tuberculosis (TB) can result in Drug-Induced Liver Injury (DILI) since hepatotoxic metabolites are formed during the biotransformation of isoniazid (INH). DILI can be related to the genetic profile of the patient. Single nucleotide polymorphisms in the CYP2E1 gene and GSTM1 and GSTT1 deletion polymorphisms have been associated with adverse events caused by INH.


OBJECTIVE
To characterize the genetic polymorphisms of CYP2E1, GSTT1 and GSTM1 in TB carriers.


DESIGN
This is an observational prospective cohort study of 45 patients undergoing treatment of TB. PCR-RFLP and multiplex-PCR were used.


RESULTS
The distribution of genotypic frequency in the promoter region (CYP2E1 gene) was: 98% wild genotype and 2% heterozygous. Intronic region: 78% wild genotype; 20% heterozygous and 2% homozygous variant. GST enzyme genes: 24% Null GSTM1 and 22% Null GSTT1. Patients with any variant allele of the CYP2E1 gene were grouped in the statistical analyses.


CONCLUSION
Patients with the CYP2E1 variant genotype or Null GSTT1 showed higher risk of presenting DILI (p=0.09; OR: 4.57; 95% CI: 0.75-27.6). Individuals with both genotypes had no increased risk compared to individuals with one genotype.
['Santos|Eliana Abreu|EA|', 'Gonçalves|José Carlos Saraiva|JCS|', 'Fleury|Marcos K|MK|', 'Kritski|Afrânio L|AL|', 'Oliveira|Martha M|MM|', 'Velasque|Luciane S|LS|', 'E Silva|José Roberto Lapa|JRL|', 'Estrela|Rita de Cássia E|RCE|']
D000293:Adolescent D000328:Adult D000368:Aged D000369:Aged, 80 and over D000995:Antitubercular Agents D056486:Chemical and Drug Induced Liver Injury D019392:Cytochrome P-450 CYP2E1 D003577:Cytochrome P-450 Enzyme System D000072467:Cytochrome P450 Family 2 D005260:Female D020022:Genetic Predisposition to Disease D005838:Genotype D006801:Humans D008099:Liver D008297:Male D008875:Middle Aged D011110:Polymorphism, Genetic D011446:Prospective Studies D014397:Tuberculosis, Pulmonary D055815:Young Adult
Hepatotoxicity Adverse event Induced liver injury from treatment of tuberculosis Polymorphisms of CYP2E1 and GST Pulmonary tuberculosis