Effects of Genetic Polymorphisms of Drug Transporter ABCB1 (MDR1) and Cytochrome P450 Enzymes CYP2A6, CYP2B6 on Nicotine Addiction and Smoking Cessation

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Muderrisoglu A., BABAOĞLU E., Korkmaz E. T., Ongun M. C., KARABULUT E., İSKİT A. B., ...Daha Fazla

FRONTIERS IN GENETICS, cilt.11, 2020 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 11
  • Basım Tarihi: 2020
  • Doi Numarası: 10.3389/fgene.2020.571997
  • Dergi Adı: FRONTIERS IN GENETICS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, EMBASE, Veterinary Science Database, Directory of Open Access Journals
  • Anahtar Kelimeler: nicotine, genetic polymorphism, addiction, P-glycoprotein, cytochrome P450 enzymes, P-GLYCOPROTEIN FUNCTION, TRANSDERMAL NICOTINE, METABOLITE RATIO, GENOTYPE, IMPACT, PHARMACOLOGY, ASSOCIATION, DISPOSITION, VARIANTS, EFFICACY
  • Hacettepe Üniversitesi Adresli: Evet

Özet

Objectives To determine the effects of genetic polymorphisms of ABCB1 (MDR1), CYP2A6, CYP2B6 on smoking status, and clinical outcomes of smoking cessation therapies in a Turkish population. Methods 130 smokers and 130 non-smokers were recruited. Individuals who never smoked were described as non-smokers. 130 smokers were treated with nicotine replacement therapy (NRT) (n = 40), bupropion (n = 47), bupropion + NRT (n = 15), and varenicline (n = 28). Smokers were checked by phone after 12 weeks of treatment whether they were able to quit smoking or not. Genotyping and phenotyping were performed. Results Cessation rates were as follows; 20.0% for NRT, 29.8% for bupropion, 40.0% for bupropion + NRT, 57.1% for varenicline (p = 0.013). The frequency of ABCB1 1236TT-2677TT-3435TT haplotype was significantly higher in non-smokers as compared to smokers (21.5% vs. 10.8, respectively; p = 0.018). Neither smoking status nor smoking cessation rates were associated with genetic variants of CYP2A6 (p = 0.652, p = 0.328, respectively), or variants of CYP2B6 (p = 0.514, p = 0.779, respectively). Conclusion Genetic variants of the drug transporter ABCB1 and the 1236TT-2677TT-3435TT haplotype was significantly associated with non-smoking status. Neither ABCB1 nor CYP2A6, CYP2B6 genetic variants were associated with smoking cessation rates at the 12th week of drug treatment.