title: Polymorphisms of IL12RB2 May Affect the Natural History of Primary Biliary Cholangitis: A Single Centre Study.
abstract: 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= 0.0009 andp= 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,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.
authors.affiliation: Department of Medical Biology, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Urszula
authors.initials: U
authors.lastname: Wasik
authors.affiliation: Translational Medicine Group, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Ewa
authors.identifier: 0000-0001-8740-5243
authors.initials: E
authors.lastname: Wunsch
authors.affiliation: Inova Diagnostics, San Diego, CA, USA.
authors.forename: Gary L
authors.identifier: 0000-0001-8992-1866
authors.initials: GL
authors.lastname: Norman
authors.affiliation: The Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece.
authors.forename: Eirini I
authors.identifier: 0000-0003-1978-4602
authors.initials: EI
authors.lastname: Rigopoulou
authors.affiliation: The Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece; Liver Sciences, Division of Liver Transplantation and Mucosal Biology, King's College London School of Medicine, Denmark Hill Campus, London SE5 9RS, UK.
authors.forename: Dimitrios P
authors.initials: DP
authors.lastname: Bogdanos
authors.affiliation: Translational Medicine Group, Pomeranian Medical University, Szczecin, Poland; Liver and Internal Medicine Unit, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Piotr
authors.identifier: 0000-0002-1817-0724
authors.initials: P
authors.lastname: Milkiewicz
authors.affiliation: Department of Medical Biology, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Małgorzata
authors.identifier: 0000-0002-2064-0545
authors.initials: M
authors.lastname: Milkiewicz
mesh_terms: D000328:Adult; D000483:Alleles; D001323:Autoantibodies / Q000097:blood*; D004247:DNA; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000276:immunology*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D053707:Receptors, Interleukin-12 / Q000235:genetics*
chemical_list: D001323:Autoantibodies; C508439:IL12RB2 protein, human; D053707:Receptors, Interleukin-12; D004247:DNA