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HLA-DRB1 and HLA-DQB1 genetic diversity modulates response to lithium in bipolar affective disorders
S. Le Clerc, L. Lombardi, BT. Baune, AT. Amare, KO. Schubert, L. Hou, SR. Clark, S. Papiol, M. Cearns, U. Heilbronner, F. Degenhardt, F. Tekola-Ayele, YH. Hsu, T. Shekhtman, M. Adli, N. Akula, K. Akiyama, R. Ardau, B. Arias, JM. Aubry, L....
Jazyk angličtina Země Velká Británie
Typ dokumentu časopisecké články, práce podpořená grantem
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- MeSH
- alely MeSH
- bipolární porucha farmakoterapie genetika MeSH
- dospělí MeSH
- farmakogenetika MeSH
- frekvence genu MeSH
- genetická predispozice k nemoci * MeSH
- genetická variace MeSH
- genotyp MeSH
- haplotypy MeSH
- HLA-DQ beta řetězec genetika MeSH
- HLA-DRB1 řetězec genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- lithium terapeutické užití MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Bipolar affective disorder (BD) is a severe psychiatric illness, for which lithium (Li) is the gold standard for acute and maintenance therapies. The therapeutic response to Li in BD is heterogeneous and reliable biomarkers allowing patients stratification are still needed. A GWAS performed by the International Consortium on Lithium Genetics (ConLiGen) has recently identified genetic markers associated with treatment responses to Li in the human leukocyte antigens (HLA) region. To better understand the molecular mechanisms underlying this association, we have genetically imputed the classical alleles of the HLA region in the European patients of the ConLiGen cohort. We found our best signal for amino-acid variants belonging to the HLA-DRB1*11:01 classical allele, associated with a better response to Li (p < 1 × 10-3; FDR < 0.09 in the recessive model). Alanine or Leucine at position 74 of the HLA-DRB1 heavy chain was associated with a good response while Arginine or Glutamic acid with a poor response. As these variants have been implicated in common inflammatory/autoimmune processes, our findings strongly suggest that HLA-mediated low inflammatory background may contribute to the efficient response to Li in BD patients, while an inflammatory status overriding Li anti-inflammatory properties would favor a weak response.
Bipolar Center Wiener Neustadt Medical Faculty Sigmund Freud University Vienna Austria
Center for Molecular Medicine Karolinska University Hospital Stockholm Sweden
Centre for Human Genetics University of Marburg Marburg Germany
Centre Investigation Clinique CIC Henri Mondor Université Paris Est Créteil 94010 Créteil France
Centro de Investigación Biomédica en Red de Salud Mental Instituto de Salud Carlos 3 Madrid Spain
Centro de Investigación Biomédica en Salud Mental Madrid Spain
Department of Adult Psychiatry Poznan University of Medical Sciences Poznan Poland
Department of Biomedical Sciences University of Cagliari Cagliari Italy
Department of Clinical Neurosciences Karolinska Institutet Stockholm Sweden
Department of Health Sciences Research Mayo Clinic Rochester MN USA
Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm Sweden
Department of Mental Health Johns Hopkins Bloomberg School of Public Health Baltimore MD USA
Department of Molecular Medicine and Surgery Karolinska Institute Stockholm Sweden
Department of Pharmacology Dalhousie University Halifax NS Canada
Department of Psychiatry and Behavioral Sciences Johns Hopkins University Baltimore MD USA
Department of Psychiatry and Psychology Mayo Clinic Rochester MN USA
Department of Psychiatry and Psychotherapy Ludwig Maximilian University Munich Munich Germany
Department of Psychiatry Dalhousie University Halifax NS Canada
Department of Psychiatry Dokkyo Medical University School of Medicine Mibu Tochigi Japan
Department of Psychiatry Hokkaido University Graduate School of Medicine Sapporo Japan
Department of Psychiatry Lindner Center of Hope University of Cincinnati Mason OH USA
Department of Psychiatry Melbourne Medical School The University of Melbourne Melbourne Australia
Department of Psychiatry Mood Disorders Unit HUG Geneva University Hospitals Geneva Switzerland
Department of Psychiatry Osaka University Graduate School of Medicine Osaka Japan
Department of Psychiatry University of California San Diego La Jolla CA USA
Department of Psychiatry University of Campania 'Luigi Vanvitelli' Naples Italy
Department of Psychiatry University of Münster Münster Germany
Department of Psychiatry University of Perugia Perugia Italy
Department of Psychiatry VA San Diego Healthcare System San Diego CA USA
Discipline of Psychiatry School of Medicine University of Adelaide Adelaide SA Australia
Douglas Mental Health University Institute McGill University Montreal QC Canada
Fondation FondaMental Créteil France
HSL Institute for Aging Research Harvard Medical School Boston MA USA
Human Genomics Research Group Department of Biomedicine University Hospital Basel Basel Switzerland
Institut de Biomedicina de la Universitat de Barcelona Barcelona Spain
Institute of Medical Genetics and Pathology University Hospital Basel Basel Switzerland
Institute of Neuroscience and Medicine Research Center Jülich Jülich Germany
Mental Health Research Group IMIM Hospital del Mar Barcelona Catalonia Spain
Mental Health Services Northern Adelaide Local Health Network Adelaide SA Australia
Montreal Neurological Institute and Hospital McGill University Montreal QC Canada
Mood Disorders Center of Ottawa Ottawa ON Canada
National Institute of Mental Health Klecany Czech Republic
Neuroscience Research Australia Sydney NSW Australia
Office of Mental Health VA San Diego Healthcare System San Diego CA USA
Plateforme de Ressources Biologiques HU Henri Mondor 94010 Créteil France
Program for Quantitative Genomics Harvard School of Public Health Boston MA USA
Psychiatric Genetic Unit Poznan University of Medical Sciences Poznan Poland
School of Medical Sciences University of New South Wales Sydney NSW Australia
School of Psychiatry University of New South Wales Sydney NSW Australia
Service de Psychiatrie Hôpital Charles Perrens Bordeaux France
The Neuromodulation Unit McGill University Health Centre Montreal QC Canada
Unit of Clinical Pharmacology Hospital University Agency of Cagliari Cagliari Italy
Unitat de Zoologia 1 Antropologia Biològica University of Barcelona CIBERSAM Barcelona Spain
Citace poskytuje Crossref.org
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- $a HLA-DRB1 and HLA-DQB1 genetic diversity modulates response to lithium in bipolar affective disorders / $c S. Le Clerc, L. Lombardi, BT. Baune, AT. Amare, KO. Schubert, L. Hou, SR. Clark, S. Papiol, M. Cearns, U. Heilbronner, F. Degenhardt, F. Tekola-Ayele, YH. Hsu, T. Shekhtman, M. Adli, N. Akula, K. Akiyama, R. Ardau, B. Arias, JM. Aubry, L. Backlund, AK. Bhattacharjee, F. Bellivier, A. Benabarre, S. Bengesser, JM. Biernacka, A. Birner, C. Brichant-Petitjean, P. Cervantes, HC. Chen, C. Chillotti, S. Cichon, C. Cruceanu, PM. Czerski, N. Dalkner, A. Dayer, M. Del Zompo, JR. DePaulo, B. Étain, S. Jamain, P. Falkai, AJ. Forstner, L. Frisen, MA. Frye, JM. Fullerton, S. Gard, JS. Garnham, FS. Goes, M. Grigoroiu-Serbanescu, P. Grof, R. Hashimoto, J. Hauser, S. Herms, P. Hoffmann, E. Jiménez, JP. Kahn, L. Kassem, PH. Kuo, T. Kato, JR. Kelsoe, S. Kittel-Schneider, E. Ferensztajn-Rochowiak, B. König, I. Kusumi, G. Laje, M. Landén, C. Lavebratt, SG. Leckband, A. Tortorella, M. Manchia, L. Martinsson, MJ. McCarthy, SL. McElroy, F. Colom, V. Millischer, M. Mitjans, FM. Mondimore, P. Monteleone, CM. Nievergelt, MM. Nöthen, T. Novák, C. O'Donovan, N. Ozaki, U. Ösby, A. Pfennig, JB. Potash, A. Reif, E. Reininghaus, GA. Rouleau, JK. Rybakowski, M. Schalling, PR. Schofield, BW. Schweizer, G. Severino, PD. Shilling, K. Shimoda, C. Simhandl, CM. Slaney, C. Pisanu, A. Squassina, T. Stamm, P. Stopkova, M. Maj, G. Turecki, E. Vieta, J. Veeh, SH. Witt, A. Wright, PP. Zandi, PB. Mitchell, M. Bauer, M. Alda, M. Rietschel, FJ. McMahon, TG. Schulze, JL. Spadoni, W. Boukouaci, JR. Richard, P. Le Corvoisier, C. Barrau, JF. Zagury, M. Leboyer, R. Tamouza
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- $a Bipolar affective disorder (BD) is a severe psychiatric illness, for which lithium (Li) is the gold standard for acute and maintenance therapies. The therapeutic response to Li in BD is heterogeneous and reliable biomarkers allowing patients stratification are still needed. A GWAS performed by the International Consortium on Lithium Genetics (ConLiGen) has recently identified genetic markers associated with treatment responses to Li in the human leukocyte antigens (HLA) region. To better understand the molecular mechanisms underlying this association, we have genetically imputed the classical alleles of the HLA region in the European patients of the ConLiGen cohort. We found our best signal for amino-acid variants belonging to the HLA-DRB1*11:01 classical allele, associated with a better response to Li (p < 1 × 10-3; FDR < 0.09 in the recessive model). Alanine or Leucine at position 74 of the HLA-DRB1 heavy chain was associated with a good response while Arginine or Glutamic acid with a poor response. As these variants have been implicated in common inflammatory/autoimmune processes, our findings strongly suggest that HLA-mediated low inflammatory background may contribute to the efficient response to Li in BD patients, while an inflammatory status overriding Li anti-inflammatory properties would favor a weak response.
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- $a Cearns, Micah $u Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, SA, Australia
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- $a Heilbronner, Urs $u Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Nußbaumstr. 7, 80336, Munich, Germany
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- $a Degenhardt, Franziska $u Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany
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- 700 1_
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- 700 1_
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- 700 1_
- $a Severino, Giovanni $u Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy
- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
- $a Pisanu, Claudia $u Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy
- 700 1_
- $a Squassina, Alessio $u Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy
- 700 1_
- $a Stamm, Thomas $u Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany
- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
- $a Spadoni, Jean-Louis $u Laboratoire Génomique, Bio-Informatique et Chimie Moléculaire (EA7528), Conservatoire National des Arts et Métiers, HESAM Université, 292, rue Saint Martin, 75003, Paris, France
- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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