title: Association between toll-like receptor 2 gene diversity and early-onset bipolar disorder.
abstract: BACKGROUND
  Toll-like receptor 2 (TLR2) molecules play a pivotal role in innate immune responses by their ability to recognize and sense a wide repertoire of infectious and endogenous cellular structural elements. Here we evaluated whether genetic variants in TLR2 influence the age of the disease onset in bipolar disorder (BD).
  
  
  METHODS
  DNAs from 571 BD patients 229 early-onset (EO-BD) and 342 late-onset (LO-BD) and 199 healthy controls (HC) were analyzed for the following TLR2 polymorphisms: the 5'-UTR -196 to -174 insertion/deletion (ins/del), the intron 1 rs4696480 A/T, and the exon 3 rs3804099 C/T and rs3804100 C/T. PHASE software was used for haplotype reconstruction. Genetic associations were examined using a chi-square test.
  
  
  RESULTS
  We found that the TLR2 rs3804099 TT was significantly more prevalent in EO-BD than in LO-BD patients (corrected p (pc)=0.024). After excluding family history of psychiatric disorders, we also found that the TLR2 rs4696480 TT genotype was significantly more prevalent in EO-BD as compared to LO-BD and controls (pc=0.002 and 0.002). Homozygous state for the insTTT haplotype, carrying the above mentioned risk genotypes, was significantly more frequent in EO-BD than in LO-BD patients (pc=0.007) and in EO-BD without family history of psychiatric disorders as compared to (i) those with positive history (pc=0.03), (ii) with LO-BD without family history (pc=0.001) and (iii) with HC (pc=0.009).
  
  
  CONCLUSIONS
  Confirmation by replication in independent BD cohorts is warranted.
  
  
  CONCLUSIONS
  Our data suggest the potential role of TLR2 genetic variants in the pathogen-mediated susceptibility to BD.
authors.affiliation: INSERM, U1160, Hôpital Saint Louis, Paris F75010, France; Fondation FondaMental, Créteil F94000 France.
authors.forename: José
authors.initials: J
authors.lastname: Oliveira
authors.affiliation: INSERM, U955, Psychiatrie Génétique, Créteil F94000, France; Université Paris-Est, Faculté de Médecine, Créteil F94000, France; AP-HP, Pôle de Psychiatrie, Hôpitaux Universitaires Henri Mondor, Créteil F94000, France; Fondation FondaMental, Créteil F94000 France.
authors.forename: Nora
authors.initials: N
authors.lastname: Hamdani
authors.affiliation: INSERM, U1160, Hôpital Saint Louis, Paris F75010, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Busson
authors.affiliation: INSERM, U955, Psychiatrie Génétique, Créteil F94000, France; Université Paris-Est, Faculté de Médecine, Créteil F94000, France; AP-HP, Pôle de Psychiatrie, Hôpitaux Universitaires Henri Mondor, Créteil F94000, France; Fondation FondaMental, Créteil F94000 France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Etain
authors.affiliation: INSERM, U1160, Hôpital Saint Louis, Paris F75010, France; Fondation FondaMental, Créteil F94000 France.
authors.forename: Meriem
authors.initials: M
authors.lastname: Bennabi
authors.affiliation: INSERM, U1160, Hôpital Saint Louis, Paris F75010, France; Laboratoire Jean Dausset and LabEx Transplantex, Hôpital Saint Louis, Avenue Claude Vellefaux, Paris F75010, France.
authors.forename: Kahina
authors.initials: K
authors.lastname: Amokrane
authors.affiliation: INSERM, U1160, Hôpital Saint Louis, Paris F75010, France.
authors.forename: Wahid
authors.initials: W
authors.lastname: Boukouaci
authors.affiliation: Laboratoire Jean Dausset and LabEx Transplantex, Hôpital Saint Louis, Avenue Claude Vellefaux, Paris F75010, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Fortier
authors.affiliation: Laboratoire Jean Dausset and LabEx Transplantex, Hôpital Saint Louis, Avenue Claude Vellefaux, Paris F75010, France.
authors.forename: François
authors.initials: F
authors.lastname: Marzais
authors.affiliation: Laboratoire Jean Dausset and LabEx Transplantex, Hôpital Saint Louis, Avenue Claude Vellefaux, Paris F75010, France.
authors.forename: Djaouida
authors.initials: D
authors.lastname: Bengoufa
authors.affiliation: INSERM, U955, Psychiatrie Génétique, Créteil F94000, France; Université Paris-Est, Faculté de Médecine, Créteil F94000, France; AP-HP, Pôle de Psychiatrie, Hôpitaux Universitaires Henri Mondor, Créteil F94000, France; Fondation FondaMental, Créteil F94000 France.
authors.forename: Frank
authors.initials: F
authors.lastname: Bellivier
authors.affiliation: INSERM, U955, Psychiatrie Génétique, Créteil F94000, France; Université Paris-Est, Faculté de Médecine, Créteil F94000, France; AP-HP, Pôle de Psychiatrie, Hôpitaux Universitaires Henri Mondor, Créteil F94000, France; Fondation FondaMental, Créteil F94000 France.
authors.forename: Chantal
authors.initials: C
authors.lastname: Henry
authors.affiliation: Service de Psychiatrie et Psychologie Clinique, CHU de Nancy, Hôpitaux de Brabois, F54500 Vandoeuvre Les Nancy, France; Fondation FondaMental, Créteil F94000 France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Kahn
authors.affiliation: INSERM, U1160, Hôpital Saint Louis, Paris F75010, France; Laboratoire Jean Dausset and LabEx Transplantex, Hôpital Saint Louis, Avenue Claude Vellefaux, Paris F75010, France; Fondation FondaMental, Créteil F94000 France; Université Paris Diderot, Sorbonne Paris-Cité, Paris F75013, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Charron
authors.affiliation: INSERM, U1160, Hôpital Saint Louis, Paris F75010, France.
authors.forename: Rajagopal
authors.initials: R
authors.lastname: Krishnamoorthy
authors.affiliation: Inserm, Centre d'Investigation Clinique 006 et Plateforme de Ressources Biologiques, Hôpital Henri-Mondor, Créteil F94000, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Le Corvoisier
authors.affiliation: INSERM, U955, Psychiatrie Génétique, Créteil F94000, France; Université Paris-Est, Faculté de Médecine, Créteil F94000, France; AP-HP, Pôle de Psychiatrie, Hôpitaux Universitaires Henri Mondor, Créteil F94000, France; Fondation FondaMental, Créteil F94000 France.
authors.forename: Marion
authors.initials: M
authors.lastname: Leboyer
authors.affiliation: INSERM, U1160, Hôpital Saint Louis, Paris F75010, France; Laboratoire Jean Dausset and LabEx Transplantex, Hôpital Saint Louis, Avenue Claude Vellefaux, Paris F75010, France; Fondation FondaMental, Créteil F94000 France; Université Paris Diderot, Sorbonne Paris-Cité, Paris F75013, France.
authors.forename: Ryad
authors.initials: R
authors.lastname: Tamouza
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D001714:Bipolar Disorder / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D051195:Toll-Like Receptor 2 / Q000235:genetics*; D055815:Young Adult
chemical_list: C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2
keywords: Bipolar disorder; Early-onset; Immunogenetics.; Innate immunity; Toll like receptor 2