Absence of Kir6.1/KCNJ8 mutations in Italian patients with abnormal coronary vasomotion.
Absence of Kir6.1/KCNJ8 mutations in Italian patients with abnormal coronary vasomotion.
复制标题
意大利冠状动脉血管舒缩异常患者不存在 Kir6.1/KCNJ8 突变。
DOI：
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发表时间：
2003
影响因子：
5.4
通讯作者：
D. Geroldi
中科院分区：
文献类型：
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作者：
E. Emanuele;C. Falcone;M. Carabela;P. Minoretti;A. D'Angelo;L. Montagna;D. Geroldi
冠状动脉血管舒缩张力的紊乱已被广泛分析，但冠状动脉血管舒缩异常的确切分子机制仍有待阐明。已有研究表明，冠状动脉血管反应性受损可能是血管平滑肌细胞缺陷的表现。最近，通过破坏Kir6.1/Kcnj8基因获得了一个人类变异型(血管痉挛)心绞痛的小鼠模型。Kir6.1/Kcnj8编码一个小孔形成的内向整流钾通道。在缺乏Kir6.1的配对蛋白Sur2的小鼠中，也有类似于变异型心绞痛的表型。为了更好地确定平滑肌型ATP敏感性钾通道在冠状动脉血管运动异常发病机制中的作用，对18例意大利冠状动脉血管运动受损患者的Kir6.1/KCNJ8基因进行了完整的突变分析。聚合酶链式反应和扩增产物直接测序。在分析的样本中没有检测到突变，因此表明Kir6.1/KCNJ8异常不是意大利人冠状动脉血管运动异常的常见原因。据我们所知，这项研究是第一次对人类Kir6.1/KCNJ8基因进行突变分析。由于冠状动脉血管运动异常的发生率存在主要的种族差异，因此需要对Kir6.1/KCNJ8基因进行进一步的突变筛查，以评估其在不同种族冠状动脉血管运动异常的发病机制中的作用。
The disturbances in coronary vasomotor tone have been extensively analyzed, but the exact molecular mechanisms underlying abnormal coronary vasomotion remain to be elucidated. It has been suggested that impaired coronary vasoreactivity can be the expression of a defect in vascular smooth muscle cells. A mouse model of human variant (vasospastic) angina has been recently obtained by disruption of Kir6.1/Kcnj8, a gene coding for a small pore-forming inward rectifier potassium channel. A phenotype resembling variant angina was also reported in mice lacking Sur2, the partner protein of Kir6.1. To better define the role of the smooth muscular ATP-sensitive potassium channels in the pathogenesis of abnormal coronary vasomotion, a complete mutational analysis of Kir6.1/KCNJ8 gene was performed in a series of 18 Italian patients with impaired coronary vasomotility. Polymerase chain reaction and direct sequencing of PCR products were done. No mutations were detected in the sample analyzed, thus suggesting that Kir6.1/KCNJ8 aberrations are not a common cause of abnormal coronary vasomotion in Italians. To the best of our knowledge, this study represents the first mutational analysis of Kir6.1/KCNJ8 gene in humans. Since major racial differences in the prevalence of abnormal coronary vasomotion have been described, further mutation screenings of Kir6.1/KCNJ8 gene are required to assess its role in the pathogenesis of impaired coronary vasomotility among various ethnic groups.