Phenotypic and pharmacogenetic evaluation of patients with thiazide-induced hyponatremia
James S Ware, Louise V Wain, Sarath K Channavajjhala, Victoria E Jackson, Elizabeth Edwards, Run Lu, Keith Siew, Wenjing Jia, Nick Shrine, Sue Kinnear, Mahli Jalland, Amanda P Henry, Jenny Clayton, Kevin M O'Shaughnessy, Martin D Tobin, Victor L Schuster, Stuart Cook, Ian P Hall, Mark Glover
Journal of Clinical Investigation | AMER SOC CLINICAL INVESTIGATION INC | Published : 2017
Thiazide diuretics are among the most widely used treatments for hypertension, but thiazide-induced hyponatremia (TIH), a clinically significant adverse effect, is poorly understood. Here, we have studied the phenotypic and genetic characteristics of patients hospitalized with TIH. In a cohort of 109 TIH patients, those with severe TIH displayed an extended phenotype of intravascular volume expansion, increased free water reabsorption, urinary prostaglandin E2 excretion, and reduced excretion of serum chloride, magnesium, zinc, and antidiuretic hormone. GWAS in a separate cohort of 48 TIH patients and 2,922 controls from the 1958 British birth cohort identified an additional 14 regions assoc..View full abstract
Awarded by British Heart Foundation
Awarded by Medical Research Council
We are grateful to David Strachan for access to the 1958 British birth cohort resource. This work was supported by an Academy of Medical Sciences grant for clinical lecturers (to JSW and MG), British Heart Foundation grant PG/09/089 (to KMO), the National Institute for Health Research (NIHR) Royal Brompton Cardiovascular Biomedical Research Unit (to JSW and SC), the Fondation Leducq (to JSW and SC), and the British Heart Foundation (to JSW and SC). MDT holds a Medical Research Council Senior Clinical Fellowship (G0902313). This work was supported by the Medical Research Council (grant numbers G510364 and G1000861). This research used the ALICE and SPECTRE High Performance Computing Facilities at the University of Leicester.