Polymorphisms of IL12RB2 May Affect the Natural History of Primary Biliary Cholangitis: A Single Centre Study.

. Recent GWAS in primary biliary cholangitis (PBC) showed strong associations with SNPs located within interleukin-12 receptor (IL12R) beta-2 gene. . We assessed whether genetic variation of is associated with laboratory and clinical features of PBC. . Genomic DNA was isolated from 306 patients with PBC and 258 age/gender-matched controls. PBC-specific anti-mitochondrial antibodies (AMA) were tested in all subjects by ELISA. Two SNPs, rs3790567 and rs6679356, of were genotyped using the MGB-TaqMan SNP assay. . Despite comparable age at diagnosis of cirrhotic and noncirrhotic PBC patients, allele A of rs3790567 and allele C of rs6679356 were overrepresented in the former rather than the latter group ( = 0.0009 and = 0.002, resp.). The risk of cirrhosis at presentation increased when allele A and allele C coexisted. AMA-M2 titres were significantly higher in AA homozygotes of rs3790567 compared to GG homozygotes (132 ± 54 versus 103 ± 62, = 0.02) and in rs6679356 when C allele was present ( = 0.038). There were no other significant associations between polymorphisms and laboratory or clinical features. . In this first study analyzing phenotypic features of PBC carriers of the polymorphisms, we found that carriers are more frequently cirrhotic at diagnosis and have significantly higher titres of AMA.