Mutational analysis of Kir6.1 in Japanese patients with coronary spastic angina

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.