The February 2020 issue of Pharmacogenetics and Genomics has a PharmGKB double feature, with the publication of our sertraline pathway and our VIP summary for CACNA1S.
The sertraline pharmacokinetic pathway, written by Scientific Curator Dr. Rachel Huddart and collaborators, is featured on the cover of the journal. Sertraline is a selective serotonin reuptake inhibitor (SSRI), which is used in the treatment of some psychiatric disorders, such as major depressive disorder. Metabolism of sertraline in the liver by CYP2C19 forms the basis of clinical guidelines from CPIC and the DPWG.
CACNA1S is a subunit of the dihydropyridine receptor and is expressed in skeletal muscle, where it plays a role in muscle contraction. Variants in CACNA1S have been linked to a number of myopathies as well as malignant hyperthermia, which can occur in some patients when exposed to inhaled anesthetics. The recent CPIC guideline forinhaled anesthetics includes recommendations based on CACNA1S variants. Our VIP summary, written by Senior Scientific Curator Dr. Katrin Sangkuhl with Dr.Robert Dirksen of the University of Rochester and former PharmGKB curator Maria Alvarellos, outlines the role of CACNA1S in both normal muscle function and in disease genetics. Key variants which have been associated with malignant hyperthermia are discussed in detail.