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

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• dc.contributor.author Le Clerc, Sigrid
• dc.contributor.author Colom, Francesc
• dc.contributor.author Tamouza, Ryad
• dc.date.accessioned 2022-07-11T06:50:28Z
• dc.date.available 2022-07-11T06:50:28Z
• dc.date.issued 2021
• dc.description.abstract 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.
• dc.format.mimetype application/pdf
• dc.identifier.citation Le Clerc S, Lombardi L, Baune BT, Amare AT, Schubert KO, Hou L, et al. HLA-DRB1 and HLA-DQB1 genetic diversity modulates response to lithium in bipolar affective disorders. Sci Rep. 2021 Sep 8; 11(1): 17823. DOI: 10.1038/s41598-021-97140-7
• dc.identifier.doi http://dx.doi.org/10.1038/s41598-021-97140-7
• dc.identifier.issn 2045-2322
• dc.identifier.uri http://hdl.handle.net/10230/53704
• dc.language.iso eng
• dc.publisher Nature Research
• dc.rights Copyright © The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.other Trastorn bipolar
• dc.subject.other Psicosi
• dc.subject.other Trastorns afectius
• dc.subject.other Liti
• dc.subject.other Marcadors bioquímics
• dc.title HLA-DRB1 and HLA-DQB1 genetic diversity modulates response to lithium in bipolar affective disorders
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion