Association Between Tuberculosis Treatment and Cyp3a4 *1b Polymorphism of the Patients

Abstract

Bakground: The level of antituberculosis (TB) agents and risk of anti-TB drug-induced liver injury could be predicted by patients' genotype polymorphism of the xenobiotic-metabolizsing enzymes. For example, detection of N-acetyltransferase 2 genotype in TB-patients is very valuable in this relation. Aim: To find the meaning of cyptochrome P-4503A4*1B (CYP3A4*1B) polymorphism in TB-patients. Materials and methods: CYP3A4*1B genotype was detected with the help of polymerase chain reaction among 105 patients with pulmonary TB. The level of rifampicin in the blood was determined spectrophotometrically. We have considered medical records at the beginning and at the end of in-patient treatment. Statistical analysis included Kruskal-Wallis, ANOVA, and Chi-square tests. Results: According to the genotype CYP3A4*1B 91.4% and 8.6% of the patients with pulmonary TB has homozygous wild-type gene (i.e., had high enzymatic activity) -AA and heterozygous AG genotype (moderate enzyme activity), correspondently. The peak of rifampicin's concentration in blood was observed 4 hrs after its intake: 16.25+/-3.92 and 15.03 +/-0.97 mcg/ml in AA and AG genotype correspondently. Thus, there was no significant difference in rifampicin concentration among TB-patients concerning CYP3A4*1B polymorphism. At the beginning of the treatment in TBpatients with AA genotype, the activity of alanine aminotransferase (ALT) and gamma-glutathione transferase (GGT) were on 53.8% and 31.8% higher than in the carriers of AG genotype, however that difference was statistically insignificant regarding to low number of AG genotypes carriers. During treatment in TB hospital in the carriers of AA genotype, the activity of ALT, AST (aspartate aminotransferase), and GGT has enhanced insignificantly, while the activity of ALT, AST, and GGT in AG genotype carriers slightly declined (P>0.05). Moreover, in the end of inpatient treatment, the rate of ALT and GGT in the carriers of AA genotype was on 123.3% (P=0.003; confidential interval = 6.77....29.73) and on 54.8% (P=0.039; confidential interval = 0.73....26.87) correspondently. Conslusion: Polymophism of CYP3A4*1B genotype is an important criterion for the development of hepatotoxicity before and during TB-treatment while it has no influence on rifampicin level in blood.