P2X7 receptor gene polymorphism analysis in rheumatoid arthritis

Summary The P2X7 receptor, a member of the P2X family of nucleotide-gated channels, is predominantly expressed by monocytic cells. The activation of this receptor has been associated with downstream-signalling cascades, resulting in the release of a number of inflammatory mediators. There are more than 815 single nucleotide polymorphisms (SNPs) that have been described in the human P2X7R gene, but only few have been functionally characterized. The main aim of this study is to determine whether P2X7R gene polymorphisms confer susceptibility to rheumatoid arthritis (RA). A total of 125 patients with RA and 158 healthy volunteers were enrolled in this study. DNA fragment was PCR amplified and sequenced on the AB 3130 Genetic Analyzer. No significant difference in allele frequencies of 489 CT, 1096 CG and 1513 AC polymorphisms, among sporadic cases of RA and healthy controls was found. However, the 1513A/C genotype was significantly associated with the presence of rheumatoid factor and anti-MCV autoantibody in RA patients. Interestingly, the genotype frequency of 1068 A/A was 0.19 in the RA group and 0.09 in control group (P = 0.025). Consequently, this polymorphism (AA) is two folds greater in the RA group compared to controls. Moreover, this polymorphism was significantly associated with mean concentration of C-reactive protein in RA patients. In contrast, 946GA and 1729 TA were not detected in both groups. As a result, these two polymorphisms are uncommon in Omani Arab population. Polymorphism at position 1068 and 1513 in the P2X7R gene might contribute to the pathogenesis of RA. Moreover, the loss-of-function SNP at position 1096 CG or the gain-of-function SNP at position 489 CT of the P2X7 gene does not appear to be a susceptibility gene locus for the development of RA. Further studies are required to confirm this finding.