title: Absence of Kir6.1/KCNJ8 mutations in Italian patients with abnormal coronary vasomotion.
abstract: 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.
authors.affiliation: Molecular Medicine Laboratory, IRCCS Policlinico San Matteo, University of Pavia, Piazzale Golgi 2, 27100 Pavia, Italy.
authors.forename: Enzo
authors.initials: E
authors.lastname: Emanuele
authors.forename: Colomba
authors.initials: C
authors.lastname: Falcone
authors.forename: Maria
authors.initials: M
authors.lastname: Carabela
authors.forename: Piercarlo
authors.initials: P
authors.lastname: Minoretti
authors.forename: Angela
authors.initials: A
authors.lastname: D'Angelo
authors.forename: Lorenza
authors.initials: L
authors.lastname: Montagna
authors.forename: Diego
authors.initials: D
authors.lastname: Geroldi
mesh_terms: D000788:Angina Pectoris, Variant / Q000235:genetics* / Q000473:pathology; D004247:DNA / Q000737:chemistry; D004252:DNA Mutational Analysis; D005091:Exons; D006801:Humans; D007438:Introns; D007558:Italy; D008957:Models, Genetic; D009154:Mutation; D016133:Polymerase Chain Reaction; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics* / Q000502:physiology*; D017422:Sequence Analysis, DNA
chemical_list: D024661:Potassium Channels, Inwardly Rectifying; D004247:DNA