Background. Recent GWAS in primary biliary cholangitis (PBC) showed strong associations with SNPs located within interleukin-12 receptor (IL12R) beta-2(IL12RB2)gene.Aims. We assessed whether genetic variation ofIL12RB2is associated with laboratory and clinical features of PBC.Methods. 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, ofIL12RB2were genotyped using the MGB-TaqMan SNP assay.Results. 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 (p=0.0009andp=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±54versus103±62,p=0.02) and in rs6679356 when C allele was present (p=0.038). There were no other significant associations betweenIL12RB2polymorphisms and laboratory or clinical features.Conclusion. In this first study analyzing phenotypic features of PBC carriers of theIL12RB2polymorphisms, we found that carriers are more frequently cirrhotic at diagnosis and have significantly higher titres of AMA.
Genetic Variation and the Natural History of Quaking Aspen
