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The HLA-G low expressor genotype is associated with protection against bipolar disorder |
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| Authors: | Monojit Debnath Marc Busson Stéphane Jamain Bruno Etain Nora Hamdani José Oliveira Wahid Boukouaci Kahina Amokrane Hélène Moins-Teisserenc Mohamed Lajnef Djaouida Bengoufa Alain Malafosse Frank Bellivier Chantal Henry Jean-Pierre Kahn Rajagopal Krishnamoorthy Dominique Charron Marion Leboyer Ryad Tamouza |
| Institution: | 1. INSERM, UMRS 940, Hôpital Saint Louis, Paris F75010, France;2. INSERM, U 955, IMRB, Psychiatrie Genetique, Créteil 94000, France;3. Laboratoire Jean Dausset, Hôpital Saint Louis, Paris F75010, France;4. Université Paris-Est-Créteil, Faculté de Medecine, Créteil 94000, France;5. AP-HP, Pôle de Psychiatrie, Groupe Hospitalier Henri Mondor, Créteil F-94000, France;6. Fondation FondaMental, Créteil, France;g Univ. Paris Diderot, Sorbonne Paris, Cité, France;h Département de Psychiatrie, Université de Genève, Genève, CH-1205 Suisse, Switzerland;i INSERM, U 763, Robert Debré Hospital, Paris, Paris F-7519, France;j Service de Psychiatrie et Psychologie Clinique, CHU de Nancy, Hôpitaux de Brabois, F-54500 Vandoeuvre Les Nancy, France |
| Abstract: | Implication of immune processes in bipolar disorder (BD) has recently gained increasing attention. Tolerogenic molecules, among which HLA-G plays a prominent role, mediate the modulation of such processes. The HLA-G locus is characterized by a high number of polymorphisms including a functionally relevant 14 base pair (bp) insertion/deletion (Ins/Del) allele affecting the HLA-G expression. Here, we analyzed the distribution of this polymorphism in 561 BD patients and 161 healthy and found that the HLA-G 14bp Ins/Ins genotype was significantly more prevalent in healthy controls than in patients (corrected p; pc = 0.032) and that the prevalence of such protective genotype is lower among patients born during the winter season as compared to those born in other periods (pc = 0.006). Possible mechanisms between low HLA G expression and resistance to infections as well as potential relationships between infections in early life and susceptibility to BD are discussed. |
| Keywords: | Bp base pair BD bipolar disorder CTLA4 cytotoxic T lymphocyte antigen 4 CI confidence interval EBV Epstein-Barr virus CMV cytomegalovirus HSV Herpes simplex virus HERV-W human endogenous retrovirus-W HTLV-1 human T cell leukemia/lymphoma virus type 1 GWAS genome-wide association studies miRNAs microRNAs OR odds ratio PCR polymerase chain reaction Treg regulatory T cells sHLA-G Soluble HLA-G |
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