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Title: | HLA-DRB1 and HLA-DQB1 genetic diversity modulates response to lithium in bipolar affective disorders |
Author: | Le Clerc, Sigrid Lombardi, Laura Baune, Bernhard T. Amare, Azmeraw T. Schubert, Klaus Oliver Clark, Scott R. Papiol, S. 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 Del Zompo, Maria DePaulo, J. Raymond Étain, Bruno Falkai, Peter Forstner, Andreas J. Tortorella, Alfonso Colom, Francesc, 1971- Mitjans Niubó, Marina Jiménez Martínez, Ester Vieta i Pascual, Eduard, 1963- |
Keywords: | Farmacogenètica Liti Trastorn bipolar Pharmacogenetics Lithium Manic-depressive illness |
Issue Date: | 8-Sep-2021 |
Publisher: | Nature Publishing Group |
Abstract: | 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. |
Note: | Reproducció del document publicat a: https://doi.org/10.1038/s41598-021-97140-7 |
It is part of: | Scientific Reports, 2021, vol. 11, num. 17823 |
URI: | http://hdl.handle.net/2445/184152 |
Related resource: | https://doi.org/10.1038/s41598-021-97140-7 |
ISSN: | 2045-2322 |
Appears in Collections: | Articles publicats en revistes (Medicina) |
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