title: TLR4 gene polymorphism associated with lifetime cigarette smoking in bipolar disorder.
abstract: Bipolar disorder (BD) is associated with an increased risk of tobacco dependence, the leading addictive substance worldwide. Toll-like receptor 4, a sensor of pathogens and of products of cellular stress and damage, is a major innate immune molecule and logical candidate gene for tobacco dependence in BD because (i) the involvement of TLR4 molecules in several substance use disorders has been suggested, (ii) and the association between the TLR4 gene and BD. We analysed herein the potential association between six TLR4 polymorphisms and lifetime tobacco smoking in 514 BD patients. Significant association between tobacco smoking and rs10759932 was found (genotype, Cochrane Armitage trend test, p=0.008, pcorrected=0.040 and alleles, p=0.008; pcorrected=0.040), where the C minor allele is associated with a protective effect, even after adjusting for confounding factors (OR=1.54 [1.04-2.30], p=0.03). Our results suggest that TLR4 gene polymorphism may act as an intermediate factor for the association between tobacco smoking addiction and BD.
authors.affiliation: INSERM UMR-S1144 - VariaPsy, Hôpital Fernand Widal, Paris 75010, France; AP-HP, DHU Pe-PSY, Pôle de Psychiatrie et d'Addictologie des Hôpitaux Universitaires, Henri Mondor, Créteil F94000, France. Electronic address: el-hadi.zerdazi@inserm.fr.
authors.forename: El-Hadi
authors.initials: EH
authors.lastname: Zerdazi
authors.affiliation: INSERM, U1160, Hôpital Saint Louis, Paris F75010, France; Fondation FondaMental, Fondation de Coopération Scientifique, Créteil, France.
authors.forename: José
authors.initials: J
authors.lastname: Oliveira
authors.affiliation: INSERM UMR-S1144 - VariaPsy, Hôpital Fernand Widal, Paris 75010, France; Université Paris Diderot, Sorbonne Paris cité, Paris, France; APHP, Département de Psychiatrie et de Médecine Addictologigue, Hôpital Fernand Widal, Paris 75010, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Vorspan
authors.affiliation: INSERM, U1160, Hôpital Saint Louis, Paris F75010, France; Fondation FondaMental, Fondation de Coopération Scientifique, Créteil, France.
authors.forename: Meriem
authors.initials: M
authors.lastname: Bennabi
authors.affiliation: Fondation FondaMental, Fondation de Coopération Scientifique, Créteil, France; Inserm U955, Psychiatrie Translationnelle, Créteil, France; Université Paris Est Créteil, Faculté de Médecine, Créteil, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Jamain
authors.affiliation: AP-HP, DHU Pe-PSY, Pôle de Psychiatrie et d'Addictologie des Hôpitaux Universitaires, Henri Mondor, Créteil F94000, France; Fondation FondaMental, Fondation de Coopération Scientifique, Créteil, France; Inserm U955, Psychiatrie Translationnelle, Créteil, France; Université Paris Est Créteil, Faculté de Médecine, Créteil, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Etain
authors.affiliation: AP-HP, DHU Pe-PSY, Pôle de Psychiatrie et d'Addictologie des Hôpitaux Universitaires, Henri Mondor, Créteil F94000, France; Fondation FondaMental, Fondation de Coopération Scientifique, Créteil, France; Inserm U955, Psychiatrie Translationnelle, Créteil, France; Université Paris Est Créteil, Faculté de Médecine, Créteil, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Leboyer
authors.affiliation: INSERM, U1160, Hôpital Saint Louis, Paris F75010, France; Fondation FondaMental, Fondation de Coopération Scientifique, Créteil, France; Laboratoire Jean Dausset, LabEx Transplantex, Hôpital Saint Louis, Paris F75010, France.
authors.forename: Ryad
authors.initials: R
authors.lastname: Tamouza
authors.affiliation: INSERM UMR-S1144 - VariaPsy, Hôpital Fernand Widal, Paris 75010, France; Fondation FondaMental, Fondation de Coopération Scientifique, Créteil, France; Université Paris Diderot, Sorbonne Paris cité, Paris, France; APHP, Département de Psychiatrie et de Médecine Addictologigue, Hôpital Fernand Widal, Paris 75010, France.
authors.forename: Frank
authors.initials: F
authors.lastname: Bellivier
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012907:Smoking / Q000453:epidemiology*; D018709:Statistics, Nonparametric; D051197:Toll-Like Receptor 4 / Q000235:genetics*
chemical_list: C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4
keywords: Addiction; Bipolar disorder; Innate immunity; TLR4; Tobacco smoking; rs10759932