Classical HLA-DRB1 and DPB1 alleles account for HLA associations with primary biliary cirrhosis.

Genes and Immunity
Pietro InvernizziItalian PBC Genetics Study Group

Abstract

Susceptibility to primary biliary cirrhosis (PBC) is strongly associated with human leukocyte antigen (HLA)-region polymorphisms. To determine if associations can be explained by classical HLA determinants, we studied Italian, 676 cases and 1440 controls, genotyped with dense single-nucleotide polymorphisms (SNPs) for which classical HLA alleles and amino acids were imputed. Although previous genome-wide association studies and our results show stronger SNP associations near DQB1, we demonstrate that the HLA signals can be attributed to classical DRB1 and DPB1 genes. Strong support for the predominant role of DRB1 is provided by our conditional analyses. We also demonstrate an independent association of DPB1. Specific HLA-DRB1 genes (*08, *11 and *14) account for most of the DRB1 association signal. Consistent with previous studies, DRB1*08 (P=1.59 × 10(-11)) was the strongest predisposing allele, whereas DRB1*11 (P=1.42 × 10(-10)) was protective. Additionally, DRB1*14 and the DPB1 association (DPB1*03:01; P=9.18 × 10(-7)) were predisposing risk alleles. No signal was observed in the HLA class 1 or class 3 regions. These findings better define the association of PBC with HLA and specifically support the role of classical HLA-DR...Continue Reading

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Citations

Aug 13, 2013·Journal of Autoimmunity·George F MellsTom H Karlsen
Sep 10, 2013·Journal of Autoimmunity·Pietro Invernizzi
Jun 14, 2013·PloS One·Xiaoming JiaPaul I W de Bakker
Mar 25, 2014·Archives of Medical Research·Man LiDian-wu Liu
Jan 1, 2013·Multiple Sclerosis and Related Disorders·Kaarina KowalecHelen Tremlett
Sep 9, 2015·Journal of Autoimmunity·G J Webb, G M Hirschfield
Dec 6, 2012·Tuberculosis Research and Treatment·Daniel S SmykEirini I Rigopoulou
Aug 8, 2015·Journal of Autoimmunity·G J WebbG M Hirschfield
Mar 17, 2015·Clinical Reviews in Allergy & Immunology·Tomohiro KatsumiYoshiyuki Ueno
Apr 16, 2013·Gastroenterology·Gideon M HirschfieldAndrew L Mason
Jun 28, 2016·Clinics and Research in Hepatology and Gastroenterology·Simona MarzoratiPietro Invernizzi
Jul 21, 2016·Immunologic Research·María-Teresa ArangoYehuda Shoenfeld
Feb 17, 2017·PloS One·Jason H KarnesDan M Roden
May 12, 2017·Science Translational Medicine·Jason H KarnesJoshua C Denny
Nov 22, 2017·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Kristjan T ÖrnolfssonEinar S Björnsson
Nov 23, 2017·Hepatology International·Ana LleoM Eric Gershwin
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Jan 3, 2019·Current Opinion in Gastroenterology·Atsushi TanakaMerrill Eric Gershwin
Dec 14, 2016·World Journal of Hepatology·Ying-Qiu Huang
Dec 1, 2012·Auto- Immunity Highlights·Ilaria BianchiPietro Invernizzi
Jun 14, 2020·Diseases·Ludovico AbenavoliPietro Invernizzi
Feb 26, 2021·Nature Communications·Seungho CookBuhm Han
Mar 9, 2019·The Surgical Clinics of North America·Christina W Lee, Sean Ronnekleiv-Kelly
Mar 7, 2021·Gastroenterology·Rosanna AsseltaPietro Invernizzi
Sep 9, 2018·Journal of Hepatology·Pedro M RodriguesJesus M Banales
May 22, 2021·Digestive and Liver Disease : Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver·Yanni LiBangmao Wang
Jul 26, 2021·European Journal of Medical Genetics·Alessio GerussiPietro Invernizzi
Jul 23, 2021·Journal of Autoimmunity·Michele GhielmettiBenedetta Terziroli Beretta-Piccoli
Aug 12, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Chen HuangLi Yang

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Methods Mentioned

BETA
chip
genotyping
PCA

Software Mentioned

SNPTEST
Beagle
PLINK
IMPUTE
EIGENSOFT
STRUCTURE

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