Human P2X7 Pore Function Predicts Allele Linkage Disequilibrium

Abstract

Background: Innate immune response amplification is achieved by leukocyte expression of the purinergic nucleotide receptor P2X₇, an extracellular nucleotide-gated pore. Previously, low P2X₇ pore activity in whole blood was associated with loss-of-function genotypes in correlation with a decreased ratio of lipopolysaccharide-stimulated tumor necrosis factor-α to interleukin-10, of relevance to a variety of infectious and inflammatory disorders. We hypothesized that evaluation of participants with discordance between the P2X7 genotype and pore status would disclose additional alleles, linkage disequilibrium, and novel functional correlates of genotype to phenotype.