The relationship between trichlormethiazide-induced hyperuricemia and the genotypes of uric acid transporters

2014 Fiscal Year Final Research Report

• Project/Area Number: 24390140
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Applied pharmacology
• Research Institution: Kyushu University
• Principal Investigator: TOSHIYUKI Sasaguri 九州大学, 医学(系)研究科(研究院), 教授 (30261209)
• Co-Investigator(Kenkyū-buntansha): MATSUMURA Kiyoshi 九州大学, 医学研究院, 准教授 (70285409) ; TAKAHASHI Fumi 九州大学, 医学研究院, 講師 (50274436) ; YOSHIHARA Tatsuya 九州大学, 医学研究院, 助教 (80419613)
• Co-Investigator(Renkei-kenkyūsha): IKEMATU Hideyuki 久留米臨床薬理クリニック ; OHTSUBO Toshio 九州大学, 病院, 講師 (30423974) ; SHIRAISHI Fumie 九州大学, 医学研究院, 技術専門員
• Research Collaborator: ARIMA Hisatomi 滋賀医科大学, アジア疫学研究センター, 特任教授 (20437784)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: チアジド / 利尿薬 / 尿酸 / 遺伝子多型 / MRP4 / ABCC4 / BCRP / ABCG2

Outline of Final Research Achievements

Diuretics often cause hyperuricemia. Suppression of the function of urate transporter may be a mechanism of diuretics-induced hyperuricemia. In the present study, we examined whether genetic mutation of MRP4, BCRP, NPT4, URAT1 and GLUT9 influence serum uric acid (SUA) level and urinary urate excretion (UUE) after administration of trichlormethiazide (TCM).
MRP4 E757K polymorphism did not influence the increase of SUA after TCM treatment, although UUE was transiently reduced in subjects with EE genotype. The increase in SUA in subjects with QX genotype in BCRP Q126X polymorphism was larger than in those with QQ genotype. However, there was no difference in UUE between QQ and QX genotypes, indicating that TCM inhibited uric acid excretion into feces in subjects with QX genotype.
Our results suggest that the predominant mechanism of TCM-induced hyperuricemia may be the inhibition of intestinal BCRP.

Free Research Field

臨床薬理学