1. Genetic factors associated with elevation of uric acid after treatment with thiazide-like diuretic in patients with essential hypertension
- Author
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Shunichi Kojima, Satoko Nakamura, Tomohiro Katsuya, Ken Sugimoto, Takuya Tsuchihashi, Takeshi Horio, Takeshi Nakahashi, Kei Kamide, Yuhei Kawano, Katsuhiro Higashiura, Hajime Nakahama, Toshiyuki Miyata, Kazuaki Shimamoto, Naonaga Hosomi, Hironori Hanada, Norio Komai, Jitsuo Higaki, Yuko Ohta, Johji Kato, Fumiki Yoshihara, Hideo Matsuura, Tetsuro Miki, Michiya Igase, Michio Ueno, Shigeto Morimoto, Tatsuo Shinagawa, Ritsuko Katabuchi, Masayoshi Soma, Kazuhiro Sase, Toshiyuki Sasaguri, Takafumi Oukura, Hiromi Rakugi, Shin Takiuchi, Kazuo Takeda, Yosikazu Miwa, Toshihiko Ishimitsu, and Yoshio Iwashima
- Subjects
Male ,medicine.medical_specialty ,Physiology ,medicine.medical_treatment ,Renal function ,Blood Pressure ,030204 cardiovascular system & hematology ,Essential hypertension ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,chemistry.chemical_compound ,Angiotensin Receptor Antagonists ,0302 clinical medicine ,Internal medicine ,Internal Medicine ,medicine ,Humans ,030212 general & internal medicine ,Amlodipine ,Diuretics ,Aged ,Cross-Over Studies ,business.industry ,Indapamide ,Middle Aged ,medicine.disease ,Calcium Channel Blockers ,Uric Acid ,Endocrinology ,Blood pressure ,Valsartan ,chemistry ,Uric acid ,Female ,Diuretic ,Essential Hypertension ,Cardiology and Cardiovascular Medicine ,business ,medicine.drug ,Genome-Wide Association Study - Abstract
We investigated changes in blood pressure (BP) and metabolic adverse effects, especially elevation of uric acid (UA), after treatment with a thiazide-like diuretic (TD) in patients with essential hypertension. Furthermore, the role of genetic factors in the elevation of UA by TD was assessed by a 500 K SNP DNA microarray. The subjects included 126 hypertensive patients (57 women and 69 men, mean age 59 ± 12 years) who registered for the GEANE (Gene Evaluation for ANtihypertensive Effects) study. After one month of the nontreatment period, TD, indapamide, angiotensin II receptor antagonist valsartan, and Ca channel blocker amlodipine were administered to all patients for 3 months each in a randomized crossover manner. BP, renal function, serum UA level, and electrolytes were measured at baseline and at the end of each treatment period. Single nucleotide polymorphisms (SNPs) associated with UA elevation after treatment with indapamide were investigated by a genome-wide association study (GWAS). Indapamide significantly decreased both office and home BP levels. Treatment with indapamide also significantly reduced the estimated glomerular filtration rate and serum potassium and increased serum UA. Patients whose UA level increased more than 1 mg/dl showed significantly higher baseline office SBP and plasma glucose and showed greater decline in renal function compared with those who showed less UA increase (
- Published
- 2019