スギモト　ケン   Ken Sugimoto   杉本　研    所属   川崎医科大学  医学部 臨床医学　総合老年医学    職種   教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Genetic factors associated with elevation of uric acid after treatment with thiazide-like diuretic in patients with essential hypertension.
掲載誌名	正式名：Hypertension research : official journal of the Japanese Society of Hypertension 略　 称：Hypertens Res ISSNコード：13484214/09169636
掲載区分	国外
巻・号・頁	43(3),pp.220-226
著者・共著者	Ohta Yuko, Kamide Kei, Hanada Hironori, Morimoto Shigeto, Nakahashi Takeshi, Takiuchi Shin, Ishimitsu Toshihiko, Tsuchihashi Takuya, Soma Masayoshi, Tomohiro Katsuya T, Sugimoto Ken, Rakugi Hiromi, Oukura Takafumi, Higaki Jitsuo, Matsuura Hideo, Shinagawa Tatsuo, Miwa Yosikazu, Sasaguri Toshiyuki, Igase Michiya, Miki Tetsuro, Takeda Kazuo, Higashiura Katsuhiro, Shimamoto Kazuaki, Katabuchi Ritsuko, Ueno Michio, Hosomi Naonaga, Kato Johji, Komai Norio, Kojima Shunichi, Sase Kazuhiro, Iwashima Yoshio, Yoshihara Fumiki, Horio Takeshi, Nakamura Satoko, Nakahama Hajime, Miyata Toshiyuki, Kawano Yuhei
発行年月	2020/03
概要	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.
DOI	10.1038/s41440-019-0356-x
PMID	31748705