Another interesting variant that recently emerged from GWAS is rs2189521, associated with primary biliary cholangitis (PBC) in the IL21 receptor gene (IL21R).97 Qiu and colleagues reported that the risk allele for PBC regulates differential IL21R expression; this variant is also highly correlated with multiple SNPs in the IL21R region, suggesting that variation in IL21R expression may explain this signal. By applying several histochemical experiments, they showed that the enhanced expression in PBC livers (in the hepatic portal tracks) of IL21R and of its ligand, IL21, support an involvement of IL21 signalling pathway deregulation in the disease mechanism.
