Circadian genes and lithium response in bipolar disorders: associations with PPARGC1A (PGC-1 α ) and RORA
| Autor: | GEOFFROY, P. A., Etain, B., Lajnef, M., Zerdazi, E. H., Brichant-Petitjean, C., Degenhardt, F., McMahon, F. J., Bellivier, F., Heilbronner, U., Hou, L., Rietschel, M., Schulze, T. G., Jamain, S., Marie-Claire, Cynthia |
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| Přispěvatelé: | Variabilité de réponse aux Psychotropes (VariaPsy - U1144), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Université Paris Diderot - Paris 7 (UPD7), Université Sorbonne Paris Cité (USPC), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Fondation FondaMental [Créteil], Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Pôle de Psychiatrie [Hôpital Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital H. Mondor - A. Chenevier, University of Bonn, Johns Hopkins University School of Medicine [Baltimore], Institut de Chimie des Milieux et Matériaux de Poitiers (IC2MP), Université de Poitiers-Institut national des sciences de l'Univers (INSU - CNRS)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institute of Psychiatric Phenomics and Genomics (IPPG), Ludwig-Maximilians-Universität München (LMU), Department of Genetic Epidemiology in Psychiatry [Mannhein], Universität Heidelberg [Heidelberg]-Central Institute of Mental Health Mannheim, Department of Psychiatry and Psychotherapy, Georg-August-University [Göttingen], Université Paris-Est Créteil Val-de-Marne - Faculté de médecine (UPEC Médecine), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Georg-August-University = Georg-August-Universität Göttingen, Optimisation Thérapeutique en Neuropsychopharmacologie (VariaPsy - U1144), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital H. Mondor - A. Chenevier, Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Centre for Environmental Research |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Adult
Male MESH: Nuclear Receptor Subfamily 1 Group F Member 1 Bipolar disorder MESH: Heat-Shock Proteins MESH: Lithium Compounds Polymorphism Single Nucleotide MESH: Bipolar Disorder [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry Molecular Biology/Genomics [q-bio.GN] clock genes Humans Genetic Predisposition to Disease MESH: Circadian Rhythm Genetic Association Studies Heat-Shock Proteins MESH: Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha MESH: Genetic Association Studies MESH: Humans MESH: Middle Aged lithium carbonate MESH: Polymorphism Single Nucleotide MESH: Genetic Predisposition to Disease Nuclear Receptor Subfamily 1 Group F Member 1 MESH: Adult MESH: Transcription Factors Middle Aged Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha MESH: Male Circadian Rhythm circadian rhythms Lithium Compounds Female lithium salts circadian genes MESH: Female Transcription Factors |
| Zdroj: | Genes, Brain and Behavior Genes, Brain and Behavior, Wiley, 2016, 15 (7), pp.660-668. ⟨10.1111/gbb.12306⟩ |
| ISSN: | 1601-1848 1601-183X |
| DOI: | 10.1111/gbb.12306⟩ |
| Popis: | International audience; Preliminary studies suggest that lithium (Li) response might be associated with some circadian gene polymorphisms, we therefore performed a pharmacogenetic study on the core clock genes in two independent samples suffering from bipolar disorder (BD) and thoroughly characterized for their Li response. Two independent Caucasian samples (165 and 58 bipolar patients) treated with Li were selected from samples recruited in a French multicenter study and assessed for their Li response using the Alda scale. The two samples were genotyped using the Human660 (H660) and OmniExpress (OE) BeadChips and gene-based association analyses of 22 core clock genes were conducted. In the first sample (H660 chip), the RAR-related orphan receptor-a gene (RORA) and the Peroxisome Proliferator-Activated Receptor Gamma, Coactivator 1 Alpha gene (PPARGC1A or PGC-1α) were significantly associated with the Li response (empirical P-value = 0.0015 and 0.04, respectively), and remained significant only for RORA after Bonferroni correction. In the second sample (OE chip), PPARGC1A was significantly associated with the Li response (empirical P-value = 0.04), and did not remain significant after Bonferroni correction. PPARGC1A is a master regulator of mitochondrial function and a key component of the endogenous clock that stimulates the expression of Bmal1 and Rev-erb-alpha through coactivation of RORA. Although the observed associations deserve further replication and investigation, our results suggest genetic associations between Li response and these two close biological partners: PPARGC1A and RORA involved in circadian rhythms and bioenergetics processes in Li response. |
| Databáze: | OpenAIRE |
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