TY  - JOUR
AU  - Bråten, Line Skute
AU  - Ingelman-Sundberg, Magnus
AU  - Jukić, Marin
AU  - Molden, Espen
AU  - Kringen, Marianne Kristiansen
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4181
AB  - Sertraline is a commonly used SSRI antidepressant drug, metabolized by CYP2C19 and CYP2B6, that exhibits a substantial interindividual variation in clinical response, of which only a part can be attributed to known genetic variants. In the current study we have examined the role of a newly discovered ultrarapid CYP2C:TG haplotype and CYP2B6 variants in order to identify the possible missing heritability for such variation in sertraline response in a large patient population (n = 840). Compared to the reference group (CYP2C19*1/*1, n = 160), sertraline exposure was increased by 128% in CYP2C19 PMs (n = 29, p < 0.001) and decreased by about 20% in CYP2C19 ultrarapid metabolizers (UMs) (homozygous carriers of CYP2C19*17 and/or CYP2C:TG haplotype) with the diplotypes CYP2C19*17/*17, CYP2C:TG/TG, or CYP2C19*17/CYP2C:TG (n = 135, p < 0.003, p = 0.022, p < 0.003, respectively). Interestingly, in patients carrying the increased function CYP2B6*4 allele, and also carrying the CYP2C19*17 and CYP2C:TG alleles (n = 10), sertraline exposure was 35.4% lower compared to the reference group, whereas in subjects being poor metabolizers (PM) in both the CYP2C19 and CYP2B6 gene, the sertraline concentrations were raised by 189%. In summary, the CYP2C19 variants including the CYP2C:TG haplotype had a significant impact on sertraline metabolism, as well as the CYP2B6*4, *6, and *9 alleles. Knowing the CYP2B6 and CYP2C19 genotype, including the CYP2C:TG haplotype status, can prospectively be useful to clinicians in making more appropriate sertraline dosing decisions.
PB  - John Wiley and Sons Inc
T2  - Clinical and Translational Science
T1  - Impact of the novel CYP2C:TG haplotype and CYP2B6 variants on sertraline exposure in a large patient population
VL  - 15
IS  - 9
SP  - 2135
EP  - 2145
DO  - 10.1111/cts.13347
ER  - 

@article{
author = "Bråten, Line Skute and Ingelman-Sundberg, Magnus and Jukić, Marin and Molden, Espen and Kringen, Marianne Kristiansen",
year = "2022",
abstract = "Sertraline is a commonly used SSRI antidepressant drug, metabolized by CYP2C19 and CYP2B6, that exhibits a substantial interindividual variation in clinical response, of which only a part can be attributed to known genetic variants. In the current study we have examined the role of a newly discovered ultrarapid CYP2C:TG haplotype and CYP2B6 variants in order to identify the possible missing heritability for such variation in sertraline response in a large patient population (n = 840). Compared to the reference group (CYP2C19*1/*1, n = 160), sertraline exposure was increased by 128% in CYP2C19 PMs (n = 29, p < 0.001) and decreased by about 20% in CYP2C19 ultrarapid metabolizers (UMs) (homozygous carriers of CYP2C19*17 and/or CYP2C:TG haplotype) with the diplotypes CYP2C19*17/*17, CYP2C:TG/TG, or CYP2C19*17/CYP2C:TG (n = 135, p < 0.003, p = 0.022, p < 0.003, respectively). Interestingly, in patients carrying the increased function CYP2B6*4 allele, and also carrying the CYP2C19*17 and CYP2C:TG alleles (n = 10), sertraline exposure was 35.4% lower compared to the reference group, whereas in subjects being poor metabolizers (PM) in both the CYP2C19 and CYP2B6 gene, the sertraline concentrations were raised by 189%. In summary, the CYP2C19 variants including the CYP2C:TG haplotype had a significant impact on sertraline metabolism, as well as the CYP2B6*4, *6, and *9 alleles. Knowing the CYP2B6 and CYP2C19 genotype, including the CYP2C:TG haplotype status, can prospectively be useful to clinicians in making more appropriate sertraline dosing decisions.",
publisher = "John Wiley and Sons Inc",
journal = "Clinical and Translational Science",
title = "Impact of the novel CYP2C:TG haplotype and CYP2B6 variants on sertraline exposure in a large patient population",
volume = "15",
number = "9",
pages = "2135-2145",
doi = "10.1111/cts.13347"
}

Bråten, L. S., Ingelman-Sundberg, M., Jukić, M., Molden, E.,& Kringen, M. K.. (2022). Impact of the novel CYP2C:TG haplotype and CYP2B6 variants on sertraline exposure in a large patient population. in Clinical and Translational Science
John Wiley and Sons Inc., 15(9), 2135-2145.
https://doi.org/10.1111/cts.13347

Bråten LS, Ingelman-Sundberg M, Jukić M, Molden E, Kringen MK. Impact of the novel CYP2C:TG haplotype and CYP2B6 variants on sertraline exposure in a large patient population. in Clinical and Translational Science. 2022;15(9):2135-2145.
doi:10.1111/cts.13347 .

Bråten, Line Skute, Ingelman-Sundberg, Magnus, Jukić, Marin, Molden, Espen, Kringen, Marianne Kristiansen, "Impact of the novel CYP2C:TG haplotype and CYP2B6 variants on sertraline exposure in a large patient population" in Clinical and Translational Science, 15, no. 9 (2022):2135-2145,
https://doi.org/10.1111/cts.13347 . .