title: Relationship between CYP2E1 polymorphism and increase of ALT activity during therapy of patients with pulmonary tuberculosis.
abstract: Association of CYP2E1 polymorphism with ALT activity increase was studied in patients with pulmonary tuberculosis receiving therapy by intermittent and daily protocols. The greatest increment of ALT activity in the group receiving therapy by intermittent protocol was seen in the patients with CYP2E1*7632TA genotype. In patients with wild homozygotic 1C/1C (6/6) genotype, ALT activity significantly increased, but remained within the normal range (p=0.048). In the group on daily regimen, activity of ALT increased significantly in patients with all genotypes identified. A more pronounced elevation surpassing the median of the upper threshold of ALT norm was observed in patients with 7632TA genotype (p=0.0051) and in patients with 7632TA or -71GT or 1C/1D genotypes in combinations with wild type alleles by other detected polymorphisms (p=0.0277). Detection of the CYP2E1 gene 7632T<A polymorphism was found to be the most informative test for prediction of the hepatotoxic reactions during therapy for tuberculosis.
authors.affiliation: Institute of Molecular Biology and Biophysics, Siberian Division of Russian Academy of Medical Sciences, Novosibirsk, Russia.
authors.forename: A V
authors.initials: AV
authors.lastname: Kudryashov
authors.forename: V A
authors.initials: VA
authors.lastname: Vavilin
authors.forename: T A
authors.initials: TA
authors.lastname: Kolpakova
authors.forename: Zh
authors.initials: Zh
authors.lastname: Mutaykhan
authors.forename: V A
authors.initials: VA
authors.lastname: Krasnov
authors.forename: V V
authors.initials: VV
authors.lastname: Lyakhovich
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism*; D000995:Antitubercular Agents / Q000627:therapeutic use; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics*; D005838:Genotype; D006801:Humans; D011110:Polymorphism, Genetic / Q000235:genetics*; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics*
chemical_list: D000995:Antitubercular Agents; D019392:Cytochrome P-450 CYP2E1; D000410:Alanine Transaminase