ArticleClinical and translational science2022
Impact of the novel CYP2C:TG haplotype and CYP2B6 variants on sertraline exposure in a large patient population.
Article in Clinical and translational science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6, CYP2C19, CYP2B6, SLC6A4, and HTR2A Genotypes and Serotonin Reuptake Inhibitor Antidepressants.Clinical pharmacology and therapeutics · 2023Guideline
- Pharmacogenetic, Clinical, Prescribing, and Demographic Predictors of Sertraline Pharmacokinetics.Pharmaceutics · 2026Article
- Precise and simultaneous SERS detection of sertraline and serotonin on large-scale sub-20 nm plasmonic gold nanocone arrays.Mikrochimica acta · 2026Article
- Influence of combined CYP2C19 and CYP2D6 phenotypes on adverse drug reactions in patients with major depressive disorder: a clinical cohort study.The pharmacogenomics journal · 2026Article
- Genetic variants ofJournal of Taibah University Medical Sciences · 2026Article
- The evolving landscape of pharmacogenomics: Current achievements and future directions.Pharmacological reviews · 2026Review
- Advances in haplotype phasing and genotype imputation.Nature reviews. Genetics · 2026Review
- Pharmacogenomics in the prediction of adverse effects of cardiovascular drugs: the PGx-CardioDrug project.Croatian medical journal · 2026Review
- Associations of CYP2B6, CYP2C19, and CYP2D6 isoforms and phenoconversion with sertraline pharmacokinetics.PloS one · 2026Article
- Article
- Applicability domain-expansion studies for machine learning models reveal new inhibitors of CYP2B6.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- French-Speaking Network of Pharmacogenetics (RNPGx) Recommendations for Clinical Use of Mavacamten.Clinical pharmacology and therapeutics · 2025Review
- Pharmacogenomic insights in psychiatric care: uncovering novel actionability, allele-specific CYP2D6 copy number variation, and phenoconversion in 15,000 patients.Molecular psychiatry · 2024Article
- IsGenes · 2024Article
- Influence of novel CYP2C-haplotype on proton pump inhibitor pharmacokinetics in children.Clinical and translational science · 2024Article
- Population pharmacokinetic approach to guide personalized sertraline treatment in Chinese patients.Heliyon · 2024Article
- Sudden-Onset Acute Obsessive-Compulsive Disorder Associated with Streptococcus and Brain MRI Hyperintensity in a Young Adult.Healthcare (Basel, Switzerland) · 2024Article
- Pharmacogenetic and clinical predictors of voriconazole concentration in hematopoietic stem cell transplant recipients receiving CYP2C19-guided dosing.The pharmacogenomics journal · 2023Article
- Impact of CYP2C:TG Haplotype on CYP2C19 Substrates Clearance In Vivo, Protein Content, and In Vitro Activity.Clinical pharmacology and therapeutics · 2023Article
- Pharmacogenomics in practice: a review and implementation guide.Frontiers in pharmacology · 2023Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
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) but 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.
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