Identification of rs11615992 as a novel regulatory SNP for human P2RX7 by allele-specific expression

P2RX7 (purinergic receptor P2X 7) is an important membrane ion channel and involved in multiple physiological processes. One non-synonymous SNP on P2RX7, rs3751143, had been proven to reduce ion channel function and further associated with multiple diseases. However, it was still unclear whether there were other cis-regulatory elements for P2RX7, which might further contribute to related diseases. Allele-specific expression (ASE) is a robust and sensitive approach to identify the potential functional region in human genome. In the current study, we measured ASE on rs3751143 in lung tissues and observed a consistent excess of A allele over C (P = 0.001), which indicated that SNP(s) in linkage disequilibrium (LD) could regulate P2RX7 expression. By analyzing the 1000 genomes project data for Chinese, one SNP locating ~ 5 kb away and downstream of P2RX7, rs11615992, was disclosed to be in strong LD with rs3751143. The dual-luciferase assay confirmed that rs11615992 could alter target gene expression in lung cell line. Through chromosome conformation capture, it was verified that the region surrounding rs11615992 could interact with P2RX7 promoter and effect as an enhancer. By chromatin immunoprecipitation, the related transcription factor POU2F1 (POU class 2 homeobox 1) was recognized to bind the region spanning rs11615992. Our work identified a novel long-distance cis-regulatory SNP for P2RX7, which might contribute to multiple diseases.