Aims: 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.
Methods: Lipopolysaccharide- and ATP-stimulated interleukin-1β production was determined in the presence or absence of GSK1370319A in blood culture from 32 prospectively genotyped subjects.
Results: 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).
Conclusions: Leukocyte P2X₇ receptors had significantly altered pharmacodynamic responses to a specific antagonist (GSK1370319A), directly related to SNP genotype.
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| http://dx.doi.org/10.1111/j.1365-2125.2012.04200.x | DOI Listing |
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