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

Maria Simakova, Zhanna Mironova, Vasiliy Trofimov, Vasiliy Belash, Elena Iantchina, Michael Dubina
European Respiratory Journal 2011 38: p439; DOI:
Maria Simakova
1Hospital Therapy, I.P. Pavlov Medical State University, St. Petersburg, Russian Federation
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Zhanna Mironova
1Hospital Therapy, I.P. Pavlov Medical State University, St. Petersburg, Russian Federation
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Vasiliy Trofimov
1Hospital Therapy, I.P. Pavlov Medical State University, St. Petersburg, Russian Federation
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Vasiliy Belash
1Hospital Therapy, I.P. Pavlov Medical State University, St. Petersburg, Russian Federation
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Elena Iantchina
2Department of Molecule and Gene Technologies, I.P. Pavlov Medical State University, St. Petersburg, Russian Federation
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Michael Dubina
2Department of Molecule and Gene Technologies, I.P. Pavlov Medical State University, St. Petersburg, Russian Federation
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Abstract

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<0.001; OR=6.6; CI95% 3.2-9.6). Mean daily dose of oral GCS (oGCS) was higher in patients with CC genotype if compared with geterozygous ones: 2.86 mg/day vs 1.86 mg/day (p=0.041).

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Lung function in SDBA patients with different C3435T genotypes of MDR1 gene

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.

  • © 2011 ERS
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Pharmacogenetic control of bronchial obstruction in steroid depend asthma (SDBA) patients
Maria Simakova, Zhanna Mironova, Vasiliy Trofimov, Vasiliy Belash, Elena Iantchina, Michael Dubina
European Respiratory Journal Sep 2011, 38 (Suppl 55) p439;

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Pharmacogenetic control of bronchial obstruction in steroid depend asthma (SDBA) patients
Maria Simakova, Zhanna Mironova, Vasiliy Trofimov, Vasiliy Belash, Elena Iantchina, Michael Dubina
European Respiratory Journal Sep 2011, 38 (Suppl 55) p439;
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