Pharmacogenetic control of bronchial obstruction in steroid depend asthma (SDBA) patients

Multidrug resistance gene (MDR1) encodes P-glycoprotein 170 (Pgp170), which realize efflux of glucocorticosteroids (GCS) from the cell. C3435T of gene MDR1 in SDBA patients is supposed to be associated with dose of GCS, their anti-inflammatory activity, degree of bronchial obstruction. Methods: Blood samples were taken from 40 SDBA patients and 103 controls. Genotypes were analyzed using PCR-RLFP method. Results: Homozygous 3435C in SDBA patients were observed more frequently, than in controls: 35% (n=14) vs 8% (n=9) (χ2=15.56, p In patients with allele C bronchial obstruction was less severe. However, if compared with TT genotype, post-broncholytic increase of velocity characteristics and Sgaw was not so marked. Conclusion: Patients with allele C require higher oGCS doses, probably, due to enhanced activity of Pgp170 and accelerated GCS efflux. In patients with TT genotype significant obstruction may be due to inadequate oGCS dose, while reversibility of distal obstruction may be due to intact function of bronchial smooth muscles and their sensitivity to GCS.