Genetic factors associated with elevation of uric acid after treatment with thiazide-like diuretic in patients with essential hypertension

Yuko Ohta, Kei Kamide, Hironori Hanada, Shigeto Morimoto, Takeshi Nakahashi, Shin Takiuchi, Toshihiko Ishimitsu, Takuya Tsuchihashi, Masayoshi Soma, T. Tomohiro Katsuya, Ken Sugimoto, Hiromi Rakugi, Takafumi Oukura, Jitsuo Higaki, Hideo Matsuura, Tatsuo Shinagawa, Yosikazu Miwa, Toshiyuki Sasaguri, Michiya Igase, Tetsuro MikiKazuo Takeda, Katsuhiro Higashiura, Kazuaki Shimamoto, Ritsuko Katabuchi, Michio Ueno, Naonaga Hosomi, Johji Kato, Norio Komai, Shunichi Kojima, Kazuhiro Sase, Yoshio Iwashima, Fumiki Yoshihara, Takeshi Horio, Satoko Nakamura, Hajime Nakahama, Toshiyuki Miyata, Yuhei Kawano

研究成果: ジャーナルへの寄稿記事

抜粋

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 (<1 mg/dl). Some SNPs strongly associated with an increase in UA after treatment with indapamide were identified. This study is the first report on SNPs associated with UA elevation after TD treatment. This information may be useful for the prevention of adverse effects after treatment with TD.

元の言語英語
ページ(範囲)220-226
ページ数7
ジャーナルHypertension Research
43
発行部数3
DOI
出版物ステータス出版済み - 3 1 2020

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All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

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