Tomita Hirofumi, Sasaki Satoko, Osanai Tomohiro, Nakano Takao, Higuma Takumi, Yokoyama Jin, Hanada Hiroyuki, Yasujima Minoru, Okumura Ken
The Second Department of Internal Medicine, Hirosaki University School of Medicine, Hirosaki 036-8562, Japan.
Int J Mol Med. 2006 Oct;18(4):589-91.
The etiology of coronary spastic angina (CSA) remains uncertain. Mice lacking the gene encoding the inwardly rectifying K(+) channel Kir6.1 were developed as an animal model of CSA. We investigated whether mutation in the coding region of the Kir6.1 gene is detected in Japanese patients with CSA. The study population included 19 Japanese patients with CSA (10 men and 9 women with a mean age of 61+/-14 years). Mutational analysis of the coding region of Kir6.1 was performed by direct sequencing. We found no missense or nonsense mutations in these samples, but we found in one female CSA patient, a single base substitution (C to T) at nucleotide position 111 in exon 2 of the coding region, which was heterozygous and did not cause amino acid substitution (Ile37Ile, silent mutation). In the remaining 18 patients, no base substitution was detected in the coding region of the Kir6.1 gene. No mutation that alters primary structure of Kir6.1 was detected in Japanese patients with CSA. The results indicate that abnormality in the primary structure of Kir6.1 may not be involved in the genetic pathogenesis of CSA in humans.
冠状动脉痉挛性心绞痛（CSA）的病因仍不明确。缺乏编码内向整流钾通道Kir6.1基因的小鼠被培育为CSA的动物模型。我们调查了在日本CSA患者中是否能检测到Kir6.1基因编码区的突变。研究对象包括19名日本CSA患者（10名男性和9名女性，平均年龄61±14岁）。通过直接测序对Kir6.1编码区进行突变分析。我们在这些样本中未发现错义或无义突变，但在一名女性CSA患者中，编码区第2外显子核苷酸位置111处发现单个碱基替换（C到T），此为杂合突变且未导致氨基酸替换（Ile37Ile，沉默突变）。在其余18名患者中，未在Kir6.1基因编码区检测到碱基替换。在日本CSA患者中未检测到改变Kir6.1一级结构的突变。结果表明，Kir6.1一级结构异常可能与人类CSA的遗传发病机制无关。
