Genetic predictors of thiazide-induced serum potassium changes in nondiabetic hypertensive patients.
Thiazide diuretics are associated with an increased risk of hypokalemia. However, pharmacogenetic markers of thiazide-induced changes in serum potassium are not well studied. The aim of this study was to investigate possible predictors of serum potassium changes after thiazide treatment. Nondiabetic hypertensive patients with a systolic blood pressure of ⩾140 or a diastolic blood pressure of ⩾90 mm Hg were enrolled in our study. After 2 weeks of lifestyle modification and diet instruction, patients with persistently elevated blood pressure were given 50 mg of hydrochlorothiazide every morning for 2 weeks. Twenty single-nucleotide polymorphism (SNP) markers were selected from two candidate genes, SLC12A3 and WNK1. Serum potassium levels were checked before and after hydrochlorothiazide treatment. A total of 75 patients eventually qualified for enrollment in our study. They received 50 mg of hydrochlorothiazide every morning for 2 weeks. Six SNPs in WNK1 (rs11064524, rs4980973, rs12581940, rs880054, rs953361, and rs10849582) were correlated with decreases in serum potassium. None of the SLC12A3 polymorphisms were correlated with decreases in serum potassium. After Bonferroni's correction, only rs4980973 was correlated with decreases in serum potassium (corrected P=0.014). Multivariate stepwise linear regression analysis revealed that the changes in serum potassium levels were independently associated with the baseline potassium level (β=-0.587, 95% confidence interval=-0.875--0.299, P=0.0001) and WNK1 rs4980973 (A/A and A/G vs. G/G, β=-0.418, 95% confidence interval=-0.598--0.237, P=0.00002). In conclusion, the baseline potassium level and the WNK1 rs4980973 polymorphism were independent predictors of decreases in serum potassium after short-term hydrochlorothiazide treatment in nondiabetic hypertensive patients.
1] Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China [2] Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China [3] Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan, Republic of China [4] Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan, Republic of China.
Chin-Chou
CC
Huang
1] Environment-Omics-Disease Research Centre, China Medical University Hospital, Taichung, Taiwan, Republic of China [2] Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan, Republic of China.
Chia-Min
CM
Chung
Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan, Republic of China.
Shuen-Iu
SI
Hung
1] Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China [2] Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan, Republic of China [3] Healthcare and Management Center, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China [4] Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China.
Hsin-Bang
HB
Leu
Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China.
Liang-Yu
LY
Lin
1] Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China [2] Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan, Republic of China [3] Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China.
Po-Hsun
PH
Huang
1] Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China [2] Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan, Republic of China [3] Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China.
Tao-Cheng
TC
Wu
1] Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China [2] Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China [3] Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan, Republic of China [4] Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China.
Shing-Jong
SJ
Lin
1] Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, Republic of China [2] Institute of Epidemiology, School of Public Health, National Taiwan University, Taipei, Taiwan, Republic of China.
Wen-Harn
WH
Pan
1] Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China [2] Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China [3] Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan, Republic of China [4] Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan, Republic of China.
Jaw-Wen
JW
Chen
D000328:Adult; D000368:Aged; D005260:Female; D005838:Genotype; D006801:Humans; D006852:Hydrochlorothiazide / Q000009:adverse effects / Q000627:therapeutic use; D006973:Hypertension / Q000097:blood* / Q000188:drug therapy / Q000235:genetics*; D007008:Hypokalemia / Q000139:chemically induced / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011188:Potassium / Q000097:blood*; D011446:Prospective Studies; D049993:Sodium Chloride Symporter Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D014883:Water-Electrolyte Imbalance / Q000139:chemically induced / Q000235:genetics
D049993:Sodium Chloride Symporter Inhibitors; D006852:Hydrochlorothiazide; D011188:Potassium