Cardiovascular Drug Research Center, Institute of Health and Environmental Medicine, Academy of Military Medical Sciences, Beijing, China.
Acta Pharmacol Sin. 2011 Aug;32(8):1078-84. doi: 10.1038/aps.2011.85. Epub 2011 Jul 18.
To study the relationship between the antihypertensive response of iptakalim and KCNJ11 polymorphisms in Chinese Han hypertensive patients.
One hundred sixty two Chinese Han hypertensive patients were administered iptakalim (5 or 10 mg/d, po) for 8 weeks. Before the treatment and 24 h after completing the treatment blood pressure (BP) was measured. Genotyping was performed using direct sequencing.
Four common A190A, E23K, I337V and 3'UTR +62 G/A polymorphisms were found in KCNJ11. The E23K, I337V and 3'UTR +62 G/A polymorphisms were in complete linkage disequilibrium, and I337V was used as a representative. There were no significant differences in age, body mass index, sex, baseline systolic BP (SBP) and diastolic BP (DBP) among the 3 genotypes for the four polymorphisms. Significant association was found between SBP response and the polymorphisms (adjusted regression coefficient: 3.5 [1.2] mmHg; P=0.003 for the A190A polymorphism; adjusted regression coefficient: 3.1 [1.2] mmHg; P=0.012 for the I337V polymorphism). The patients with TT genotype for A190A polymorphism had higher clinical efficacy than those with CC genotype.
The results suggest the KCNJ11 polymorphisms are associated with the SBP-lowering response of short-term iptakalim therapy in Chinese Han hypertensive patients.
研究中国汉族高血压患者伊潘立酮降压反应与 KCNJ11 多态性的关系。
162 例中国汉族高血压患者给予伊潘立酮（5 或 10mg/d，po）治疗 8 周。治疗前和治疗结束后 24 小时测量血压（BP）。采用直接测序法进行基因分型。
在 KCNJ11 中发现了 4 种常见的 A190A、E23K、I337V 和 3'UTR+62G/A 多态性。E23K、I337V 和 3'UTR+62G/A 多态性完全连锁不平衡，I337V 作为代表。这四种多态性在年龄、体重指数、性别、基线收缩压（SBP）和舒张压（DBP）方面在 3 种基因型之间无显著差异。SBP 反应与多态性之间存在显著相关性（调整后的回归系数：3.5[1.2]mmHg；A190A 多态性 P=0.003；调整后的回归系数：3.1[1.2]mmHg；I337V 多态性 P=0.012）。A190A 多态性 TT 基因型患者的临床疗效高于 CC 基因型患者。
结果表明，KCNJ11 多态性与中国汉族高血压患者短期伊潘立酮治疗的 SBP 降低反应有关。
