Genetic predictors of theophylline efficacy and safety in children with bronchial asthma

Abstract

Aim. To study the prevalence of С734A polymorphic marker of CYP1А2 genotype in population of children of different ethnical groups, and to estimate the phenotypic activity of CYP3A4 izoenzyme by age and gender for further increasing the theophylline treatment safety in children with bronchial asthma. Methods. 250 healthy children aged from 1 to 10 years from different ethnical groups (Russians, Kalmyks, Ingush, Chechens, Tatars). Each ethnical group consisted of 50 children. CYP1А2 izoenzyme genotype (by С734A polymorphic marker) was detected by polymerase chain reaction. CYP3A4 izoenzyme of liver cytochrome P 450 activity was measured by calculating urine 6-β-hydrocortisone level to urine cortisol level ratio. Urine 6-β-hydrocortisone and cortisol levels were measured by high precision Liquid chromatography-mass spectrometry. Results. It is the first time when high prevalence of CYP1А2 genotype was reported in children of 5 different nationalities living in Astrakhan region, associated both with slow and rapid CYP1А2 substrate drug metabolism, showing the importance of further individual studies on CYP1А2 genotype polymorphism. Age and gender-related features of CYP3A4 izoenzyme phenotype activity, that should be taken into account while choosing the most effective and safe methylxanthines dosing, were revealed. Conclusion. Before the long-term drug therapy of bronchial asthma using theophylline it is rational to investigate CYP1А2 gene polymorphism and CYP3A4 izoenzyme phenotype activity to increase treatment safety.

Keywords

biotransformation / children / cytochrome P 450 / bronchial asthma / ethnical pharmacogenetics / gene polymorphism

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RIGHTS & PERMISSIONS

Kantemirova B.I., Starodubtsev A.K., Sychev D.A., Griganov V.I.