title: Misoprostol-induced fever and genetic polymorphisms in drug transporters SLCO1B1 and ABCC4 in women of Latin American and European ancestry.
abstract: OBJECTIVE
  Misoprostol, a prostaglandin analogue used for the treatment of postpartum hemorrhage and termination of pregnancy, can cause high fevers. Genetic susceptibility may play a role in misoprostol-induced fever.
  
  
  METHODS
  Body temperature of women treated with misoprostol for termination of pregnancy in the UK (n = 107) and for postpartum hemorrhage in Ecuador (n = 50) was measured. Genotyping for 33 single nucleotide polymorphisms in 15 candidate genes was performed. Additionally, we investigated the transport of radiolabeled misoprostol acid across biological membranes in vitro.
  
  
  RESULTS
  The ABCC4 single nucleotide polymorphism rs11568658 was associated with misoprostol-induced fever. Misoprostol acid was transported across a blood-brain barrier model by MRP4 and SLCO1B1.
  
  
  CONCLUSIONS
  Genetic variability in ABCC4 may contribute to misoprostol-induced fever in pregnant women. Original submitted 21 January 2015; Revision submitted 24 April 2015.
authors.affiliation: The Wolfson Centre for Personalised Medicine, Department of Molecular & Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Block A, Waterhouse Buildings, 1-5 Brownlow Street, Ashton Street, Liverpool, L69 3GL, UK.
authors.forename: Ana
authors.initials: A
authors.lastname: Alfirevic
authors.affiliation: Gynuity Health Projects, NY, USA.
authors.forename: Jill
authors.initials: J
authors.lastname: Durocher
authors.affiliation: Department of Women's & Children's Health, University of Liverpool, Liverpool Women's Hospital, Liverpool, UK.
authors.forename: Anisa
authors.initials: A
authors.lastname: Elati
authors.affiliation: Hospital Gineco-Obstétrico Isidro Ayora, Av Colombia N14-66 y Sodiro Quito, Ecuador.
authors.forename: Wilfrido
authors.initials: W
authors.lastname: León
authors.affiliation: The Wolfson Centre for Personalised Medicine, Department of Molecular & Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Block A, Waterhouse Buildings, 1-5 Brownlow Street, Ashton Street, Liverpool, L69 3GL, UK.
authors.forename: David
authors.initials: D
authors.lastname: Dickens
authors.affiliation: The Wolfson Centre for Personalised Medicine, Department of Molecular & Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Block A, Waterhouse Buildings, 1-5 Brownlow Street, Ashton Street, Liverpool, L69 3GL, UK.
authors.forename: Steffen
authors.initials: S
authors.lastname: Rädisch
authors.affiliation: The Wolfson Centre for Personalised Medicine, Department of Molecular & Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Block A, Waterhouse Buildings, 1-5 Brownlow Street, Ashton Street, Liverpool, L69 3GL, UK.
authors.forename: Helen
authors.initials: H
authors.lastname: Box
authors.affiliation: The Wolfson Centre for Personalised Medicine, Department of Molecular & Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Block A, Waterhouse Buildings, 1-5 Brownlow Street, Ashton Street, Liverpool, L69 3GL, UK.
authors.forename: Marco
authors.initials: M
authors.lastname: Siccardi
authors.affiliation: The Wolfson Centre for Personalised Medicine, Department of Molecular & Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Block A, Waterhouse Buildings, 1-5 Brownlow Street, Ashton Street, Liverpool, L69 3GL, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Curley
authors.affiliation: The Wolfson Centre for Personalised Medicine, Department of Molecular & Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Block A, Waterhouse Buildings, 1-5 Brownlow Street, Ashton Street, Liverpool, L69 3GL, UK.
authors.forename: George
authors.initials: G
authors.lastname: Xinarianos
authors.affiliation: The Wolfson Centre for Personalised Medicine, Department of Molecular & Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Block A, Waterhouse Buildings, 1-5 Brownlow Street, Ashton Street, Liverpool, L69 3GL, UK.
authors.forename: Arjun
authors.initials: A
authors.lastname: Ardeshana
authors.affiliation: The Wolfson Centre for Personalised Medicine, Department of Molecular & Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Block A, Waterhouse Buildings, 1-5 Brownlow Street, Ashton Street, Liverpool, L69 3GL, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Owen
authors.affiliation: The Wolfson Centre for Personalised Medicine, Department of Molecular & Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Block A, Waterhouse Buildings, 1-5 Brownlow Street, Ashton Street, Liverpool, L69 3GL, UK.
authors.forename: J Eunice
authors.initials: JE
authors.lastname: Zhang
authors.affiliation: The Wolfson Centre for Personalised Medicine, Department of Molecular & Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Block A, Waterhouse Buildings, 1-5 Brownlow Street, Ashton Street, Liverpool, L69 3GL, UK.
authors.forename: Munir
authors.initials: M
authors.lastname: Pirmohamed
authors.affiliation: Department of Women's & Children's Health, University of Liverpool, Liverpool Women's Hospital, Liverpool, UK.
authors.forename: Zarko
authors.initials: Z
authors.lastname: Alfirevic
authors.affiliation: Department of Women's & Children's Health, University of Liverpool, Liverpool Women's Hospital, Liverpool, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Weeks
authors.affiliation: Gynuity Health Projects, NY, USA.
authors.forename: Beverly
authors.initials: B
authors.lastname: Winikoff
mesh_terms: D000020:Abortifacient Agents, Nonsteroidal / Q000009:adverse effects* / Q000378:metabolism; D000328:Adult; D001812:Blood-Brain Barrier / Q000378:metabolism; D001831:Body Temperature; D002460:Cell Line; D005260:Female; D005334:Fever / Q000139:chemically induced* / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007843:Latin America; D027381:Liver-Specific Organic Anion Transporter 1; D016595:Misoprostol / Q000009:adverse effects* / Q000378:metabolism; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D027361:Organic Anion Transporters / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D019106:Postoperative Hemorrhage / Q000150:complications / Q000188:drug therapy / Q000235:genetics; D011247:Pregnancy; D044465:White People
chemical_list: D000020:Abortifacient Agents, Nonsteroidal; D027381:Liver-Specific Organic Anion Transporter 1; D016595:Misoprostol; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D027361:Organic Anion Transporters; C073492:ABCC4 protein, human; C503999:SLCO1B1 protein, human
keywords: adverse drug reactions; drug transporters; misoprostol; misoprostol-induced fever; obstetrics; pharmacogenetics; postpartum hemorrhage; reproductive medicine