PMID- 22573116 OWN - NLM STAT- MEDLINE DCOM- 20130110 LR - 20221207 IS - 1476-5470 (Electronic) IS - 1466-4879 (Print) IS - 1466-4879 (Linking) VI - 13 IP - 6 DP - 2012 Sep TI - Classical HLA-DRB1 and DPB1 alleles account for HLA associations with primary biliary cirrhosis. PG - 461-8 LID - 10.1038/gene.2012.17 [doi] AB - 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 x 10(-11)) was the strongest predisposing allele, whereas DRB1*11 (P=1.42 x 10(-10)) was protective. Additionally, DRB1*14 and the DPB1 association (DPB1*03:01; P=9.18 x 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-DRB1 and DPB1 genes and alleles in susceptibility to PBC. FAU - Invernizzi, P AU - Invernizzi P AD - Department of Medicine, Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, Davis, CA 95616, USA. FAU - Ransom, M AU - Ransom M FAU - Raychaudhuri, S AU - Raychaudhuri S FAU - Kosoy, R AU - Kosoy R FAU - Lleo, A AU - Lleo A FAU - Shigeta, R AU - Shigeta R FAU - Franke, A AU - Franke A FAU - Bossa, F AU - Bossa F FAU - Amos, C I AU - Amos CI FAU - Gregersen, P K AU - Gregersen PK FAU - Siminovitch, K A AU - Siminovitch KA FAU - Cusi, D AU - Cusi D FAU - de Bakker, P I W AU - de Bakker PI FAU - Podda, M AU - Podda M FAU - Gershwin, M E AU - Gershwin ME FAU - Seldin, M F AU - Seldin MF CN - Italian PBC Genetics Study Group LA - eng GR - R01 DK091823/DK/NIDDK NIH HHS/United States GR - K08AR055688/AR/NIAMS NIH HHS/United States GR - K08 AR055688-01A1S1/AR/NIAMS NIH HHS/United States GR - K08 AR055688-04/AR/NIAMS NIH HHS/United States GR - K08 AR055688/AR/NIAMS NIH HHS/United States GR - R01DK091823/DK/NIDDK NIH HHS/United States GR - R01 DK056839/DK/NIDDK NIH HHS/United States GR - K08 AR055688-05/AR/NIAMS NIH HHS/United States PT - Journal Article PT - Multicenter Study PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20120510 PL - England TA - Genes Immun JT - Genes and immunity JID - 100953417 RN - 0 (HLA-DP beta-Chains) RN - 0 (HLA-DPB1 antigen) RN - 0 (HLA-DRB1 Chains) SB - IM MH - Case-Control Studies MH - Gene Frequency MH - Genetic Predisposition to Disease MH - Genome-Wide Association Study MH - HLA-DP beta-Chains/*genetics MH - HLA-DRB1 Chains/*genetics MH - Humans MH - Italy MH - Liver Cirrhosis, Biliary/*genetics/*immunology MH - Oligonucleotide Array Sequence Analysis MH - Polymorphism, Single Nucleotide MH - Risk Factors MH - White People/genetics PMC - PMC3423484 MID - NIHMS368582 COIS- Disclosures: The authors declare no potential conflicts of interest. FIR - Almasio, Piero L IR - Almasio PL FIR - Alvaro, Domenico IR - Alvaro D FIR - Andreone, Pietro IR - Andreone P FIR - Andriulli, Angelo IR - Andriulli A FIR - Barlassina, Cristina IR - Barlassina C FIR - Benedetti, Antonio IR - Benedetti A FIR - Bernuzzi, Francesca IR - Bernuzzi F FIR - Bianchi, Ilaria IR - Bianchi I FIR - Bragazzi, Maria Consiglia IR - Bragazzi MC FIR - Brunetto, Maurizia IR - Brunetto M FIR - Bruno, Savino IR - Bruno S FIR - Caliari, Lisa IR - Caliari L FIR - Casella, Giovanni IR - Casella G FIR - Civardi, Fabiola IR - Civardi F FIR - Coco, Barbara IR - Coco B FIR - Colli, Agostino IR - Colli A FIR - Colombo, Massimo IR - Colombo M FIR - Colombo, Silvia IR - Colombo S FIR - Cursaro, Carmela IR - Cursaro C FIR - Croce, Lory Saveria IR - Croce LS FIR - Crosignani, Andrea IR - Crosignani A FIR - Donato, Francesca IR - Donato F FIR - Fabris, Luca IR - Fabris L FIR - Ferrari, Carlo IR - Ferrari C FIR - Floreani, Annarosa IR - Floreani A FIR - Galli, Andrea IR - Galli A FIR - Grattagliano, Ignazio IR - Grattagliano I FIR - Lazzari, Roberta IR - Lazzari R FIR - Macaluso, Fabio IR - Macaluso F FIR - Marra, Fabio IR - Marra F FIR - Marzioni, Marco IR - Marzioni M FIR - Mattalia, Alberto IR - Mattalia A FIR - Montanari, Renzo IR - Montanari R FIR - Morini, Lorenzo IR - Morini L FIR - Morisco, Filomena IR - Morisco F FIR - Moroni, Luca IR - Moroni L FIR - Muratori, Luigi IR - Muratori L FIR - Muratori, Paolo IR - Muratori P FIR - Niro, Grazia IR - Niro G FIR - Picciotto, Antonio IR - Picciotto A FIR - Portincasa, Piero IR - Portincasa P FIR - Prati, Daniele IR - Prati D FIR - Prisco, Cleofe IR - Prisco C FIR - Rosina, Floriano IR - Rosina F FIR - Rossi, Sonia IR - Rossi S FIR - Selmi, Carlo IR - Selmi C FIR - Spinzi, Giancarlo IR - Spinzi G FIR - Strazzabosco, Mario IR - Strazzabosco M FIR - Tarallo, Sonia IR - Tarallo S FIR - Tiribelli, Claudio IR - Tiribelli C FIR - Toniutto, Pierluigi IR - Toniutto P FIR - Vinci, Maria IR - Vinci M FIR - Zuin, Massimo IR - Zuin M EDAT- 2012/05/11 06:00 MHDA- 2013/01/11 06:00 PMCR- 2013/03/01 CRDT- 2012/05/11 06:00 PHST- 2012/05/11 06:00 [entrez] PHST- 2012/05/11 06:00 [pubmed] PHST- 2013/01/11 06:00 [medline] PHST- 2013/03/01 00:00 [pmc-release] AID - gene201217 [pii] AID - 10.1038/gene.2012.17 [doi] PST - ppublish SO - Genes Immun. 2012 Sep;13(6):461-8. doi: 10.1038/gene.2012.17. Epub 2012 May 10.