Document Detail


A polymorphism in the protein kinase C gene PRKCB is associated with α2-adrenoceptor-mediated vasoconstriction.
MedLine Citation:
PMID:  23337848     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: α2-Adrenoceptors (α2-AR) mediate both constriction and dilatation of blood vessels. There is considerable interindividual variability in dorsal hand vein (DHV) constriction responses to α2-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 α2-AR-mediated vascular constriction induced by the selective α2-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 β 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 β may contribute toward the interindividual variation in DHV constriction responses to α2-AR activation by the agonist dexmedetomidine.
Authors:
Jussi P Posti; Perttu Salo; Saku Ruohonen; Laura Valve; Mordechai Muszkat; Gbenga G Sofowora; Daniel Kurnik; Charles Michael Stein; Markus Perola; Mika Scheinin; Amir Snapir
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Pharmacogenetics and genomics     Volume:  23     ISSN:  1744-6880     ISO Abbreviation:  Pharmacogenet. Genomics     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-01-28     Completed Date:  2013-07-05     Revised Date:  2014-03-06    
Medline Journal Info:
Nlm Unique ID:  101231005     Medline TA:  Pharmacogenet Genomics     Country:  United States    
Other Details:
Languages:  eng     Pagination:  127-34     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Dexmedetomidine / pharmacology
Finland
Genome-Wide Association Study
Humans
Polymorphism, Single Nucleotide*
Protein Kinase C / genetics*
Protein Kinase C beta
Receptors, Adrenergic, alpha-2 / physiology*
Reference Values
Vasoconstriction / physiology*
Grant Support
ID/Acronym/Agency:
GM 5MO1-RR00095/GM/NIGMS NIH HHS; M01 RR000095/RR/NCRR NIH HHS; P01 HL056693/HL/NHLBI NIH HHS; P01 HL56693/HL/NHLBI NIH HHS; U01 HL065962/HL/NHLBI NIH HHS; U01GM61374/GM/NIGMS NIH HHS; U01HL65962/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Receptors, Adrenergic, alpha-2; 67VB76HONO/Dexmedetomidine; EC 2.7.11.13/Protein Kinase C; EC 2.7.11.13/Protein Kinase C beta
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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