Dual Roles for the TSPYL Family in Mediating Serotonin Transport and the Metabolism of Selective Serotonin Reuptake Inhibitors in Patients with Major Depressive Disorder

Sisi Qin, Andy R. Eugene, Duan Liu, Lingxin Zhang, Drew Neavin, Joanna M. Biernacka, Jia Yu, Richard M. Weinshilboum, Liewei Wang

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

We previously reported that testis-specific Y-encoded-like protein (TSPYLs) are transcription regulators for CYP3A4, CYP2C9, and CYP2C19. Here, we observed dual roles for TSPYLs in mediating serotonin transport and the metabolism of selective serotonin reuptake inhibitors (SSRIs) in patients with major depressive disorder (MDD). The widely prescribed SSRIs, citalopram, and escitalopram are metabolized mainly by CYP2C19. The TSPYL1 rs3828743 single nucleotide polymorphism (SNP), which decreases its suppression of CYP2C19 expression, was associated with rapid escitalopram metabolism and worse treatment response in the Mayo PGRN-AMPS clinical trial. We also found that TSPYLs can regulate expression of the serotonin transporter protein, SLC6A4, and, in turn, serotonin transport into cells. The SNPs in tight linkage disequilibrium with the TSPYL1 rs10223646 SNP were significantly correlated with baseline severity of depression in patients with MDD in the Sequenced Treatment Alternatives to Relieve Depression and International SSRI Pharmacogenomics Consortium clinical trials. Our findings suggest that genetic variation in TSPYL genes may be novel indicators for baseline severity of depression and SSRI poor response.

Original languageEnglish (US)
Pages (from-to)662-670
Number of pages9
JournalClinical pharmacology and therapeutics
Volume107
Issue number3
DOIs
StatePublished - Mar 1 2020

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Fingerprint Dive into the research topics of 'Dual Roles for the TSPYL Family in Mediating Serotonin Transport and the Metabolism of Selective Serotonin Reuptake Inhibitors in Patients with Major Depressive Disorder'. Together they form a unique fingerprint.

Cite this