Publication Date:
2019
Description:
Abstract
We previously reported that 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 (SSRI) in major depressive disorder (MDD) patients. The widely prescribed SSRIs, citalopram and escitalopram are metabolized mainly by CYP2C19. The TSPYL1 rs3828743 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 LD with the TSPYL1 rs10223646 SNP were significantly correlated with baseline severity of depression in MDD patients in the STAR*D and ISPC clinical trials. Our findings suggest that genetic variation in TSPYL genes may be novel indicators for baseline severity of depression and SSRI poor response.
Print ISSN:
0009-9236
Electronic ISSN:
1532-6535
Topics:
Chemistry and Pharmacology
,
Medicine
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