title: Molecular analysis of potassium ion channel genes in sudden death cases among patients administered psychotropic drug therapy: are polymorphisms in LQT genes a potential risk factor?
abstract: Psychotropic drugs can pose the risk of acquired long QT syndrome (LQTS). Unexpected autopsy-negative sudden death in patients taking psychotropic drugs may be associated with prolonged QT intervals and life-threatening arrhythmias. We analyzed genes that encode for cardiac ion channels and potentially associated with LQTS, examining specifically the potassium channel genes KCNQ1 and KCNH2 in 10 cases of sudden death involving patients administered psychotropic medication in which autopsy findings identified no clear cause of death. We amplified and sequenced all exons of KCNQ1 and KCNH2, identifying G643S, missense polymorphism in KCNQ1, in 6 of the 10 cases. A study analysis indicated that only 11% of 381 healthy Japanese individuals carry this polymorphism. Reports of previous functional analyses indicate that the G643S polymorphism in the KCNQ1 potassium channel protein causes mild I(Ks) channel dysfunction. Our present study suggests that administering psychotropic drug therapy to individuals carrying the G643S polymorphism may heighten the risk of prolonged QT intervals and life-threatening arrhythmias. Thus, screening for the G643S polymorphism before prescribing psychotropic drugs may help reduce the risk of unexpected sudden death.
authors.affiliation: 1] Department of Legal Medicine, Shinshu University School of Medicine, Nagano, Japan [2] Department of Biochemistry, Graduate School of Oral Medicine, Matsumoto Dental University, Nagano, Japan.
authors.forename: Sayako
authors.initials: S
authors.lastname: Kamei
authors.affiliation: Department of Legal Medicine, Shinshu University School of Medicine, Nagano, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Sato
authors.affiliation: Department of Legal Medicine, Shinshu University School of Medicine, Nagano, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Harayama
authors.affiliation: Department of Legal Medicine, Shinshu University School of Medicine, Nagano, Japan.
authors.forename: Miyako
authors.initials: M
authors.lastname: Nunotani
authors.affiliation: Department of Legal Medicine, Shinshu University School of Medicine, Nagano, Japan.
authors.forename: Kanae
authors.initials: K
authors.lastname: Takatsu
authors.affiliation: Department of Legal Medicine, Shinshu University School of Medicine, Nagano, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Shiozaki
authors.affiliation: Department of Legal Medicine, Shinshu University School of Medicine, Nagano, Japan.
authors.forename: Tokutaro
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: Department of Legal Medicine, Shinshu University School of Medicine, Nagano, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Asamura
mesh_terms: D000328:Adult; D003645:Death, Sudden; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics*; D005260:Female; D006213:Hallucinogens / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D051657:KCNQ1 Potassium Channel / Q000235:genetics*; D008133:Long QT Syndrome / Q000139:chemically induced / Q000235:genetics / Q000401:mortality; D008297:Male; D020125:Mutation, Missense; D011110:Polymorphism, Genetic; D012559:Schizophrenia / Q000188:drug therapy / Q000235:genetics / Q000401:mortality
chemical_list: D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D006213:Hallucinogens; C000606913:KCNH2 protein, human; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human