Duan Ruifeng, Cui Wenyu, Wang Hai
Cardiovascular Drug Research Center, Institute of Health and Environmental Medicine, Academy of Military Medical Sciences, Beijing 100850;
Exp Ther Med. 2011 Jul;2(4):757-760. doi: 10.3892/etm.2011.259. Epub 2011 Apr 28.
Iptakalim is a novel K(ATP) opener with antihypertensive properties. The Kir6.1 gene is one of the candidate genes that may influence the response to iptakalim in hypertensive patients. We aimed to ascertain whether a mutation in the coding region of the Kir6.1 gene is present in Chinese Han hypertensive patients. The study population included 162 Chinese Han hypertensive patients (81 men and 81 women with a mean age of 55±9 years). Mutational analysis of the coding region of Kir6.1 was performed using PCR-SSCP and direct sequencing. No missense or nonsense mutations were found in these samples, while a single base pair substitution (C to T) at nucleotide position 111 in exon 2 of the coding region was noted in four patients (one female and three male), who were all heterozygous for the mutation. This C to T substitution did not result in an amino acid substitution (Ile37Ile, silent mutation). In the remaining 158 patients, no mutation was detected. The blood pressure of these four patients carrying the I37I polymorphism was well controlled by iptakalim. No mutation that alters the primary structure of Kir6.1 was detected in Chinese Han hypertensive patients. The results indicate that abnormality in the primary structure of Kir6.1 is not involved in the genetic pathogenesis of essential hypertension in Chinese Han hypertensive patients and has no effect on the BP response to iptakalim treatment.
伊普卡林是一种具有降压特性的新型钾离子通道开放剂。Kir6.1基因是可能影响高血压患者对伊普卡林反应的候选基因之一。我们旨在确定中国汉族高血压患者的Kir6.1基因编码区是否存在突变。研究人群包括162名中国汉族高血压患者（81名男性和81名女性，平均年龄55±9岁）。使用PCR-SSCP和直接测序对Kir6.1编码区进行突变分析。在这些样本中未发现错义或无义突变，而在4名患者（1名女性和3名男性）中发现编码区第2外显子核苷酸位置111处有单个碱基对替换（C到T），他们均为该突变的杂合子。这种C到T的替换未导致氨基酸替换（Ile37Ile，沉默突变）。在其余158名患者中未检测到突变。这4名携带I37I多态性的患者的血压通过伊普卡林得到了良好控制。在中国汉族高血压患者中未检测到改变Kir6.1一级结构的突变。结果表明，Kir6.1一级结构异常不参与中国汉族高血压患者原发性高血压的遗传发病机制，对伊普卡林治疗的血压反应也无影响。
