HLA-DRB1 and HLA-DQB1 genetic diversity modulates response to lithium in bipolar affective disorders

Bipolar afective 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 stratifcation are still needed. A GWAS performed by the Int...

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Detalles Bibliográficos
Autores: Le Clerc, Sigrid, Lombardi, Laura, Baune, Bernhard T., Amare, Azmeraw T., Schubert, Klaus Oliver, Clark, Scott R., Papiol, Sergi, Cearns, Micah, Degenhardt, Franziska, Adl, Mazda, Akula, Nirmala, Akiyama, Kazufumi, Ardau, Raffaella, Arias Sampériz, Bárbara, Aubry, Jean-Michel, Backlund, Lena, Bhattacharjee, Abesh Kumar, Bellivier, Frank, Benabarre, Antonio, Bengesser, Susanne, Biernacka, Joanna M., Birner, Armin, Cervantes, Pablo, Chen, Hsi-Chung, Chillotti, Caterina, Cichon, Sven, Cruceanu, Cristiana, Czerski, Piotr M., Dalkner, Nina, Dayer, Alexandre, Zompo, Maria del, DePaulo, J. Raymond, Étain, Bruno, Falkai, Peter, Forstner, Andreas J., Tortorella, Alfonso, Colom, Francesc, 1971-, Mitjans Niubó, Marina, Jiménez Martínez, Esther, Vieta i Pascual, Eduard, 1963-
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/184152
Acceso en línea:https://hdl.handle.net/2445/184152
Access Level:acceso abierto
Palabra clave:Farmacogenètica
Liti
Trastorn bipolar
Pharmacogenetics
Lithium
Manic-depressive illness
Descripción
Sumario:Bipolar afective 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 stratifcation are still needed. A GWAS performed by the International Consortium on Lithium Genetics (ConLiGen) has recently identifed 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 infammatory/autoimmune processes, our fndings strongly suggest that HLA-mediated low infammatory background may contribute to the efcient response to Li in BD patients, while an infammatory status overriding Li anti-infammatory properties would favor a weak response.

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