Decreased telomere length in a subgroup of young individuals with bipolar disorders: replication in the FACE-BD cohort and association with the shelterin component POT1
Luana Spano, Cynthia Marie‐Claire, Ophélia Godin, Apolline Lebras, Cindie Courtin, Jean Laplanche, Marion Leboyer, Bruno Aouizerate, Antoine Lefrère, Raoul Belzeaux, Philippe Courtet, Émilie Olié, Caroline Dubertret, Raymund Schwan, V. Aubin, Paul Roux, Mircea Polosan, Ludovic Samalin, Émmanuel Haffen, Bruno Étain, E. Olié, Marion Leboyer, Émmanuel Haffen, Pierre‐Michel Llorca, V. Barteau, S. Bensalem, Ophélia Godin, H. Laouamri, K. Souryis, S. Hotier, Agnès Pelletier, Noëmie Drancourt, Juliana P. Sánchez, E. Saliou, C. Hebbache, J. Petrucci, L. Willaume, E. Bourdin, Frank Bellivier, Bruno Étain, Vincent Hennion, Emeline Marlinge, Pierre Lebard, B. Antoniol, A. Desage, Sébastien Gard, A. Jutant, Katia M’Baïlara, I. Minois, L. Zanouy, C. Abettan, Laurent Bardin, A. Cazals, Philippe Courtet, B. Deffinis, Déborah Ducasse, M. Gachet, Annabelle Henrion, E. Martinerie, Fanny Molière, B. Noisette, E. Olié, G. Tarquini, Jean‐Michel Azorin, Raoul Belzeaux, N. Corréard, Julia-Lou Consoloni, F. Groppi, Lauriane Lescalier, J. Montant, M. Rebattu, N. Viglianese, Renaud F. Cohen, Jean‐Pierre Kahn, Maria Milazzo, O. Wajsbrot‐Elgrabli, Thierry Bougerol, B. Fredembach, Q. Denoual, Anne Bertrand, Arnaud Pouchon, Mircea Polosan, L. Brehon, G. Bony, L Durand, V. Feuga, N. Kayser, Christine Passerieux, Paul Roux, V. Aubin, I. Cussac, Mickaël Dupont, J. Loftus, I. Medecin, Caroline Dubertret, Nicolas Mazer, C. Portalier, C. Scognamiglio, A. Bing, Paôline Laurent
Abstract
Bipolar disorder (BD) has been associated with premature cellular aging with shortened telomere length (TL) as compared to the general population. We recently identified a subgroup of young individuals with prematurely shortened TL. The aims of the present study were to replicate this observation in a larger sample and analyze the expression levels of genes associated with age or TL in a subsample of these individuals. TL was measured on peripheral blood DNA using quantitative polymerase chain reaction in a sample of 542 individuals with BD and clustering analyses were performed. Gene expression level of 29 genes, associated with aging or with telomere maintenance, was analyzed in RNA samples from a subsample of 129 individuals. Clustering analyses identified a group of young individuals (mean age 29.64 years), with shorter TL. None of the tested clinical variables were significantly associated with this subgroup. Gene expression level analyses showed significant downregulation of MYC, POT1, and CD27 in the prematurely aged young individuals compared to the young individuals with longer TL. After adjustment only POT1 remained significantly differentially expressed between the two groups of young individuals. This study confirms the existence of a subgroup of young individuals with BD with shortened TL. The observed decrease of POT1 expression level suggests a newly described cellular mechanism in individuals with BD, that may contribute to telomere shortening.