Genetic factors associated with elevation of uric acid after treatment with thiazide-like diuretic in patients with essential hypertension
Genetic factors associated with elevation of uric acid after treatment with thiazide-like diuretic in patients with essential hypertension
复制标题
原发性高血压患者噻嗪类利尿剂治疗后尿酸升高的遗传因素
DOI：
10.1038/s41440-019-0356-x
复制
发表时间：
2019
影响因子：
5.4
通讯作者：
et al. (37人中31番目)
中科院分区：
文献类型：
--
作者：
Ohta Yuko;Kamide Kei;Hanada Hironori;et al. (37人中31番目)
我们研究了原发性高血压患者接受噻嗪类利尿剂（TD）治疗后血压（BP）的变化和代谢不良反应，尤其是尿酸（UA）升高。此外，通过500 K SNP DNA微阵列评估遗传因素在TD升高UA中的作用。受试者包括126名高血压患者（57名女性和69名男性，平均年龄59 ± 12岁），他们注册了GEANE（抗高血压效应基因评价）研究。在一个月的非治疗期后，TD，吲达帕胺，血管紧张素II受体拮抗剂缬沙坦，钙通道阻滞剂缬沙坦给药3个月，所有患者在随机交叉的方式。在基线和每个治疗期结束时测量血压、肾功能、血清尿酸水平和电解质。通过全基因组关联研究（GWAS），对吲达帕胺治疗后UA升高相关的单核苷酸多态性（SNPs）进行了研究。吲达帕胺显着降低办公室和家庭BP水平。吲达帕胺治疗还显著降低了肾小球滤过率和血清钾，并增加了血清尿酸。UA水平升高超过1 mg/dl的患者与UA水平升高较少（<1 mg/dl）的患者相比，基线SBP和血糖显著升高，肾功能下降更严重。一些SNPs与吲达帕胺治疗后UA增加密切相关。本研究是首次报道TD治疗后UA升高相关的SNP。这些信息可能有助于预防TD治疗后的不良反应。
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.