title: CYP1A2 polymorphism and theophylline clearance in Korean non-smoking asthmatics.
abstract: BACKGROUND
  Theophylline is mainly metabolized by cytochrome P450 (CYP) 1A2 and CYP2E1 which show inter-individual variations. However, the underlying mechanism remains unknown in humans. We investigated the relationship between differences in theophylline clearance and genetic polymorphisms in the CYP1A2 and CYP2E1 gene in 89 Korean asthmatic patients.
  
  
  METHODS
  Polymerase chain reaction (PCR) was performed on the 5'-flanking region of those genes. PCR products were directly sequenced and confirmed using the SNaP shot method. We determined whether the detected SNPs affected gene transcription using electrophoretic mobility shift assay (EMSA). Theophylline clearance (mL/kg/h) was assessed by using a Bayesian approach.
  
  
  RESULTS
  Genetic polymorphisms were identified at 7 sites in the CYP1A2 gene and at 10 sites in the CYP2E1. Among them, subjects with genotypes (GA+AA) of the -3860G>A polymorphism were found to show higher theophylline clearance than those with genotypes GG (29.11 ± 0.91 mL/kg/h vs. 26.12 ± 0.80 mL/kg/h, p = 0.014). This polymorphic site was revealed to be a protein binding site by conducting EMSA on nuclear hepatocyte extracts.
  
  
  CONCLUSIONS
  In conclusion, increased theophylline clearance was significantly related to the -3860G>A polymorphism, which could be associated with increased CYP1A2 inducibility in Korean non-smoking asthmatics.
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul 110-799, Korea. ; Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul 110-799, Korea. ; Health Insurance Review and Assessment Service, Seoul 137-706, Korea.
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Yim
authors.forename: Hye-Ryun
authors.initials: HR
authors.lastname: Kang
authors.forename: Jae-Woo
authors.initials: JW
authors.lastname: Jung
authors.forename: Seong-Wook
authors.initials: SW
authors.lastname: Sohn
authors.forename: Sang-Heon
authors.initials: SH
authors.lastname: Cho
keywords: CYP1A2; Clearance; Cytochrome P450; Electrophoretic mobility shift assay; Polymorphism; Theophylline