Journal Article

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

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

2020

Overview

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.

• Publisher: Nature Publishing Group
• Subject: Antihypertensives / Diuretics / Hypertension / Uric acid