PMID- 25611558
OWN - NLM
STAT- MEDLINE
DCOM- 20160314
LR  - 20181113
IS  - 1476-5470 (Electronic)
IS  - 1466-4879 (Linking)
VI  - 16
IP  - 4
DP  - 2015 Jun
TI  - HLA-DRB1*03:01 and HLA-DRB1*04:01 modify the presentation and outcome in 
      autoimmune hepatitis type-1.
PG  - 247-52
LID - 10.1038/gene.2014.82 [doi]
AB  - The classical human leukocyte antigen (HLA)-DRB1*03:01 and HLA-DRB1*04:01 alleles 
      are established autoimmune hepatitis (AIH) risk alleles. To study the 
      immune-modifying effect of these alleles, we imputed the genotypes from 
      genome-wide association data in 649 Dutch AIH type-1 patients. We therefore 
      compared the international AIH group (IAIHG) diagnostic scores as well as the 
      underlying clinical characteristics between patients positive and negative for 
      these HLA alleles. Seventy-five percent of the AIH patients were 
      HLA-DRB1*03:01/HLA-DRB1*04:01 positive. HLA-DRB1*03:01/HLA-DRB1*04:01-positive 
      patients had a higher median IAIHG score than 
      HLA-DRB1*03:01/HLA-DRB1*04:01-negative patients (P<0.001). We did not observe 
      associations between HLA alleles and alanine transaminase levels (HLA-DRB1*03:01: 
      P=0.2; HLA-DRB1*04:01; P=0.5); however, HLA-DRB1*03:01 was independently 
      associated with higher immunoglobulin G levels (P=0.04). The HLA-DRB1*04:01 
      allele was independently associated with presentation at older age (P=0.03) and a 
      female predominance (P=0.04). HLA-DRB1*03:01-positive patients received 
      immunosuppressive medication and liver transplantation. In conclusion, the 
      HLA-DRB1*03:01 and HLA-DRB1*04:01 alleles are both independently associated with 
      the aggregate diagnostic IAIHG score in type-1 AIH patients, but are not 
      essential for AIH development. HLA-DRB1*03:01 is the strongest genetic modifier 
      of disease severity in AIH.
FAU - van Gerven, N M F
AU  - van Gerven NM
AD  - Department of Gastroenterology and Hepatology, VU University Medical Center, 
      Amsterdam, The Netherlands.
FAU - de Boer, Y S
AU  - de Boer YS
AD  - Department of Gastroenterology and Hepatology, VU University Medical Center, 
      Amsterdam, The Netherlands.
FAU - Zwiers, A
AU  - Zwiers A
AD  - 1] Department of Gastroenterology and Hepatology, VU University Medical Center, 
      Amsterdam, The Netherlands [2] Department of Molecular Cell Biology and 
      Immunology, VU University Medical Center, Amsterdam, The Netherlands.
FAU - Verwer, B J
AU  - Verwer BJ
AD  - Department of Gastroenterology and Hepatology, VU University Medical Center, 
      Amsterdam, The Netherlands.
FAU - Drenth, J P H
AU  - Drenth JP
AD  - Department of Gastroenterology and Hepatology, Radboud University Nijmegen 
      Medical Center, Nijmegen, The Netherlands.
FAU - van Hoek, B
AU  - van Hoek B
AD  - Department of Gastroenterology and Hepatology, Leiden University Medical Center, 
      Leiden, The Netherlands.
FAU - van Erpecum, K J
AU  - van Erpecum KJ
AD  - Department of Gastroenterology and Hepatology, University Medical Center Utrecht, 
      Utrecht, The Netherlands.
FAU - Beuers, U
AU  - Beuers U
AD  - Department of Gastroenterology and Hepatology, Academic Medical Center, 
      Amsterdam, The Netherlands.
FAU - van Buuren, H R
AU  - van Buuren HR
AD  - Department of Gastroenterology and Hepatology, Erasmus University Medical Center, 
      Rotterdam, The Netherlands.
FAU - den Ouden, J W
AU  - den Ouden JW
AD  - Department of Gastroenterology and Hepatology, Haga Hospital, The Hague, The 
      Netherlands.
FAU - Verdonk, R C
AU  - Verdonk RC
AD  - 1] University of Groningen, University Medical Center Groningen, Department of 
      Gastroenterology and Hepatology, Groningen, The Netherlands [2] Department of 
      Gastroenterology and Hepatology, St Antonius Hospital Nieuwegein, Nieuwegein, The 
      Netherlands.
FAU - Koek, G H
AU  - Koek GH
AD  - Department of Gastroenterology and Hepatology, University Medical Center 
      Maastricht, Maastricht, The Netherlands.
FAU - Brouwer, J T
AU  - Brouwer JT
AD  - Department of Gastroenterology and Hepatology, Reinier de Graaf Hospital, Delft, 
      The Netherlands.
FAU - Guichelaar, M M J
AU  - Guichelaar MM
AD  - Department of Gastroenterology and Hepatology, Medisch Spectrum Twente, Enschede, 
      The Netherlands.
FAU - Vrolijk, J M
AU  - Vrolijk JM
AD  - Department of Gastroenterology and Hepatology, Rijnstate Hospital, Arnhem, The 
      Netherlands.
FAU - Coenraad, M J
AU  - Coenraad MJ
AD  - Department of Gastroenterology and Hepatology, Leiden University Medical Center, 
      Leiden, The Netherlands.
FAU - Kraal, G
AU  - Kraal G
AD  - Department of Molecular Cell Biology and Immunology, VU University Medical 
      Center, Amsterdam, The Netherlands.
FAU - Mulder, C J J
AU  - Mulder CJ
AD  - Department of Gastroenterology and Hepatology, VU University Medical Center, 
      Amsterdam, The Netherlands.
FAU - van Nieuwkerk, C M J
AU  - van Nieuwkerk CM
AD  - Department of Gastroenterology and Hepatology, VU University Medical Center, 
      Amsterdam, The Netherlands.
FAU - Bloemena, E
AU  - Bloemena E
AD  - Department of Pathology, VU University Medical Center, Amsterdam, The 
      Netherlands.
FAU - Verspaget, H W
AU  - Verspaget HW
AD  - Department of Gastroenterology and Hepatology, Radboud University Nijmegen 
      Medical Center, Nijmegen, The Netherlands.
FAU - Kumar, V
AU  - Kumar V
AD  - University of Groningen, University Medical Center Groningen, Department of 
      Genetics, Groningen, The Netherlands.
FAU - Zhernakova, A
AU  - Zhernakova A
AD  - University of Groningen, University Medical Center Groningen, Department of 
      Genetics, Groningen, The Netherlands.
FAU - Wijmenga, C
AU  - Wijmenga C
AD  - University of Groningen, University Medical Center Groningen, Department of 
      Genetics, Groningen, The Netherlands.
FAU - Franke, L
AU  - Franke L
AD  - University of Groningen, University Medical Center Groningen, Department of 
      Genetics, Groningen, The Netherlands.
FAU - Bouma, G
AU  - Bouma G
AD  - 1] Department of Gastroenterology and Hepatology, VU University Medical Center, 
      Amsterdam, The Netherlands [2] Department of Molecular Cell Biology and 
      Immunology, VU University Medical Center, Amsterdam, The Netherlands.
CN  - Dutch Autoimmune Hepatitis Study Group
LA  - eng
PT  - Clinical Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150122
PL  - England
TA  - Genes Immun
JT  - Genes and immunity
JID - 100953417
RN  - 0 (HLA-DRB1 Chains)
RN  - 0 (HLA-DRB1*03:01 antigen)
RN  - 0 (HLA-DRB1*04:01 antigen)
RN  - 0 (Immunoglobulin G)
SB  - IM
MH  - Adult
MH  - Age of Onset
MH  - Aged
MH  - Cohort Studies
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - HLA-DRB1 Chains/*genetics/immunology
MH  - Hepatitis, Autoimmune/diagnosis/etiology/*genetics/therapy
MH  - Humans
MH  - Immunoglobulin G/blood
MH  - Liver Transplantation
MH  - Male
MH  - Middle Aged
MH  - Multivariate Analysis
MH  - Treatment Outcome
FIR - Baak, L C
IR  - Baak LC
FIR - Baven-Pronk, A M
IR  - Baven-Pronk AM
FIR - Klempt-Kropp, M
IR  - Klempt-Kropp M
FIR - van Meyel, J J M
IR  - van Meyel JJ
FIR - Linskens, R K
IR  - Linskens RK
FIR - Spanier, B W
IR  - Spanier BW
FIR - Kneppelhout, J C
IR  - Kneppelhout JC
FIR - Kuyvenhoven, J Ph
IR  - Kuyvenhoven JP
FIR - van Geenen, E J M
IR  - van Geenen EJ
FIR - Wagtmans, M J
IR  - Wagtmans MJ
FIR - Cahen, D L
IR  - Cahen DL
FIR - Wolfhagen, F H J
IR  - Wolfhagen FH
FIR - Kingma, P J
IR  - Kingma PJ
FIR - de Vree, J M L
IR  - de Vree JM
FIR - Loffeld, R J L F
IR  - Loffeld RJ
FIR - de Man, Rob A
IR  - de Man RA
FIR - Friederich, P W
IR  - Friederich PW
FIR - Schreuder, T C M A
IR  - Schreuder TC
FIR - van Milligen de Wit, A W M
IR  - van Milligen de Wit AW
FIR - Alleman, M A
IR  - Alleman MA
FIR - Bhalla, A
IR  - Bhalla A
FIR - Stadhouders, P H G M
IR  - Stadhouders PH
FIR - Verhagen, M A M T
IR  - Verhagen MA
EDAT- 2015/01/23 06:00
MHDA- 2016/03/15 06:00
CRDT- 2015/01/23 06:00
PHST- 2014/10/15 00:00 [received]
PHST- 2014/12/16 00:00 [revised]
PHST- 2014/12/16 00:00 [accepted]
PHST- 2015/01/23 06:00 [entrez]
PHST- 2015/01/23 06:00 [pubmed]
PHST- 2016/03/15 06:00 [medline]
AID - gene201482 [pii]
AID - 10.1038/gene.2014.82 [doi]
PST - ppublish
SO  - Genes Immun. 2015 Jun;16(4):247-52. doi: 10.1038/gene.2014.82. Epub 2015 Jan 22.