A polymorphism in the protein kinase C gene PRKCB is associated with α2-adrenoceptor-mediated vasoconstriction

Objectives alpha(2)-Adrenoceptors (alpha(2)-AR) mediate both constriction and dilatation of blood vessels. There is considerable interindividual variability in dorsal hand vein (DHV) constriction responses to alpha(2)-AR agonist activation. Genetic factors appear to contribute significantly to this variation. The present study was designed to identify the genetic factors contributing toward the interindividual variability in alpha(2)-AR-mediated vascular constriction induced by the selective alpha(2)-AR agonist dexmedetomidine. Methods DHV constriction responses to a local infusion of dexmedetomidine were assessed by measuring changes in vein diameter with a linear variable differential transformer. The outcome variable for constriction was log-transformed dexmedetomidine ED50. A genome-wide association study (GWAS) of 433 378 single-nucleotide polymorphisms (SNPs) was carried out for determining the sensitivity of DHV responses in 64 healthy Finnish individuals. Twenty SNPs were selected on the basis of the GWAS results and their associations with the ED50 of dexmedetomidine were tested in an independent North American study population of 68 healthy individuals. Results In both study populations (GWAS and replication samples), the SNP rs9922316 in the gene for protein kinase C type beta was consistently associated with dexmedetomidine ED50 for DHV constriction (unadjusted P = 0.00016 for the combined population). Conclusion Genetic variation in protein kinase C type beta may contribute toward the interindividual variation in DHV constriction responses to alpha(2)-AR activation by the agonist dexmedetomidine. Pharmacogenetics and Genomics 23:127-134 (c) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.