TY  - JOUR
AU  - Lenk, Hasan Çağın
AU  - Klöditz, Katharina
AU  - Johansson, Inger
AU  - Løvsletten Smith, Robert
AU  - Jukić, Marin
AU  - Molden, Espen
AU  - Ingelman-Sundberg, Magnus
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4075
AB  - The genetic background for interindividual variability of the polymorphic CYP2D6 enzyme activity remains incompletely understood and the role of NFIB genetic polymorphism for this variability was evaluated in this translational study. We investigated the effect of NFIB expression in vitro using 3D liver spheroids, Huh7 cells, and the influence of the NFIB polymorphism on metabolism of risperidone in patients in vivo. We found that NFIB regulates several important pharmacogenes, including CYP2D6. NFIB inhibited CYP2D6 gene expression in Huh7 cells and NFIB expression in livers was predominantly nuclear and reduced at the mRNA and protein level in carriers of the NFIB rs28379954 T>C allele. Based on 604 risperidone treated patients genotyped for CYP2D6 and NFIB, we found that the rate of risperidone hydroxylation was elevated in NFIB rs28379954 T>C carriers among CYP2D6 normal metabolizers, resulting in a similar rate of drug metabolism to what is observed in CYP2D6 ultrarapid metabolizers, with no such effect observed in CYP2D6 poor metabolizers lacking functional enzyme. The results indicate that NFIB constitutes a novel nuclear factor in the regulation of cytochrome P450 genes, and that its polymorphism is a predictor for the rate of CYP2D6 dependent drug metabolism in vivo.
PB  - John Wiley and Sons Inc
T2  - Clinical Pharmacology and Therapeutics
T1  - The Polymorphic Nuclear Factor NFIB Regulates Hepatic CYP2D6 Expression and Influences Risperidone Metabolism in Psychiatric Patients
DO  - 10.1002/cpt.2571
ER  - 

@article{
author = "Lenk, Hasan Çağın and Klöditz, Katharina and Johansson, Inger and Løvsletten Smith, Robert and Jukić, Marin and Molden, Espen and Ingelman-Sundberg, Magnus",
year = "2022",
abstract = "The genetic background for interindividual variability of the polymorphic CYP2D6 enzyme activity remains incompletely understood and the role of NFIB genetic polymorphism for this variability was evaluated in this translational study. We investigated the effect of NFIB expression in vitro using 3D liver spheroids, Huh7 cells, and the influence of the NFIB polymorphism on metabolism of risperidone in patients in vivo. We found that NFIB regulates several important pharmacogenes, including CYP2D6. NFIB inhibited CYP2D6 gene expression in Huh7 cells and NFIB expression in livers was predominantly nuclear and reduced at the mRNA and protein level in carriers of the NFIB rs28379954 T>C allele. Based on 604 risperidone treated patients genotyped for CYP2D6 and NFIB, we found that the rate of risperidone hydroxylation was elevated in NFIB rs28379954 T>C carriers among CYP2D6 normal metabolizers, resulting in a similar rate of drug metabolism to what is observed in CYP2D6 ultrarapid metabolizers, with no such effect observed in CYP2D6 poor metabolizers lacking functional enzyme. The results indicate that NFIB constitutes a novel nuclear factor in the regulation of cytochrome P450 genes, and that its polymorphism is a predictor for the rate of CYP2D6 dependent drug metabolism in vivo.",
publisher = "John Wiley and Sons Inc",
journal = "Clinical Pharmacology and Therapeutics",
title = "The Polymorphic Nuclear Factor NFIB Regulates Hepatic CYP2D6 Expression and Influences Risperidone Metabolism in Psychiatric Patients",
doi = "10.1002/cpt.2571"
}

Lenk, H. Ç., Klöditz, K., Johansson, I., Løvsletten Smith, R., Jukić, M., Molden, E.,& Ingelman-Sundberg, M.. (2022). The Polymorphic Nuclear Factor NFIB Regulates Hepatic CYP2D6 Expression and Influences Risperidone Metabolism in Psychiatric Patients. in Clinical Pharmacology and Therapeutics
John Wiley and Sons Inc..
https://doi.org/10.1002/cpt.2571

Lenk HÇ, Klöditz K, Johansson I, Løvsletten Smith R, Jukić M, Molden E, Ingelman-Sundberg M. The Polymorphic Nuclear Factor NFIB Regulates Hepatic CYP2D6 Expression and Influences Risperidone Metabolism in Psychiatric Patients. in Clinical Pharmacology and Therapeutics. 2022;.
doi:10.1002/cpt.2571 .

Lenk, Hasan Çağın, Klöditz, Katharina, Johansson, Inger, Løvsletten Smith, Robert, Jukić, Marin, Molden, Espen, Ingelman-Sundberg, Magnus, "The Polymorphic Nuclear Factor NFIB Regulates Hepatic CYP2D6 Expression and Influences Risperidone Metabolism in Psychiatric Patients" in Clinical Pharmacology and Therapeutics (2022),
https://doi.org/10.1002/cpt.2571 . .