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

Urszula Wasik,Dimitrios P Bogdanos,Eirini I Rigopoulou,Gary L Norman,Małgorzata Milkiewicz,Piotr Milkiewicz,Ewa Wunsch

doi:10.1155/2017/2185083

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 of IL12RB2 is 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, of IL12RB2 were 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 and p = 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 between IL12RB2 polymorphisms and laboratory or clinical features. Conclusion. In this first study analyzing phenotypic features of PBC carriers of the IL12RB2 polymorphisms, we found that carriers are more frequently cirrhotic at diagnosis and have significantly higher titres of AMA.

Highlights

Interleukin-12 (IL-12) belongs to the IL-12 family cytokines along with IL-23, IL-27, and IL-35
IL-12 exerts its immunobiological action through its binding to specific IL-12 receptors (IL-12Rs), termed IL-12Rβ1 and IL-12Rβ2, which are mapped on chromosomes 19p13.1 and 1p31.2, respectively [1,2,3]
The allele A of rs3790567 and allele C of rs6679356 were overrepresented in primary biliary cholangitis (PBC) patients compared to controls, 30.4% versus 20.7% (p = 0.0009) and 25% versus 17.2% (p = 0.0022), respectively, confirming a significant impact of IL12RB2 polymorphisms on PBC susceptibility (Table 2)

Summary

Background

Recent GWAS in primary biliary cholangitis (PBC) showed strong associations with SNPs located within interleukin receptor (IL12R) beta-2 (IL12RB2) gene. We assessed whether genetic variation of IL12RB2 is associated with laboratory and clinical features of PBC. 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 and p = 0.002, resp.). 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 between IL12RB2 polymorphisms and laboratory or clinical features. In this first study analyzing phenotypic features of PBC carriers of the IL12RB2 polymorphisms, we found that carriers are more frequently cirrhotic at diagnosis and have significantly higher titres of AMA

Introduction

Results

Methods

Discussion