Bronchial asthma (BA) pharmacogenetic profile and therapeutic resistance in slavic population

Background. MDR1 gene controls steroids (GCS) transport mechanisms, influences cell sensitivity to GCS and determines GCS treatment necessity, efficacy and complications in BA patients. Aim. To assess the role of MDR1 gene in therapeutic resistant BA (TRBA), predict GCS efficacy. Methods. Genomic DNA was extracted from peripheral leukocytes. We investigated C3435T of MDR1 gene by PCR-RFLP in 46 TRBA and 76 therapy-sensitive BA (TSBA) patients. GCRα and GCRβ expression was evaluated by RT-qPCR method. Results. In SDBA group associations were revealed between 3435CC of MDR1 gene and increased risk (IR) of GCS more than 20 mg of prednisolon daily (OR=8,40, 95%CI 1,73 – 40,71); 3435C and IR of TRBA (OR=2.89, 95%CI 1.30-6.40). In TRBA correlation between 3435T allele of MDR1 gene and number of status asthmaticus episodes in case history was revealed (Spearman R=–0,513; p=0,035; n=17), with IgE level in serum (Spearman R=–0,408; p=0,028; n=29). Correlation between MDR1 polymorphisms and isoforms of GCRb was found also in patients with mild BA course (χ 2 =6,50; df=2; p=0,039). Conclusion. MDR1 polymorphisms can be prognostic markers of therapeutic resistance and determine the strategy of high doses of GCS administration.