Referenced in: none

Automatically associated channels: Kv6.1 , SK1

Title: Effects of genetic variation in the P2RX7 gene on pharmacodynamics of a P2X(7) receptor antagonist: a prospective genotyping approach.

Authors: Simon M McHugh, Shilina Roman, Bill Davis, Annelize Koch, Alison M Pickett, Jill C Richardson, Sam R Miller, Sally Wetten, Charles J Cox, Fredrik Karpe, John A Todd, Edward T Bullmore

Journal, date & volume: Br J Clin Pharmacol, 2012 Aug , 74, 376-80

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/22295949

Abstract
To investigate the effects of two single nucleotide polymorphisms (SNPs) in the human P2X₇ receptor gene (P2RX7)--1068G>A (A348T) and 1513A>C (E496A)--on P2X₇ receptor function, using a specific receptor antagonist (GSK1370319A) and prospective genetic stratification.Lipopolysaccharide- and ATP-stimulated interleukin-1β production was determined in the presence or absence of GSK1370319A in blood culture from 32 prospectively genotyped subjects.There was approximately 6.7-fold difference (P < 0.0001) in IC₅₀ for inhibition of ATP-stimulated interleukin-1β release by GSK1370319A between individuals with the homozygous gain--(1068A) and loss-of-function (1513C) genotypes (expressing the 348T, 496E and 348A, 496A alleles, respectively).Leukocyte P2X₇ receptors had significantly altered pharmacodynamic responses to a specific antagonist (GSK1370319A), directly related to SNP genotype.