title: Polymorphism of Toll-like receptor 4 gene in bipolar disorder.
abstract: BACKGROUND
  Bipolar disorder (BD) is considered as a multifactorial disorder involving complex interactions between genetic and environmental factors, where immune dysfunction is thought to play a key etiopathogenic role. In particular, excess of winter births associated with early-life infections raise the possibility of the implication of innate immunity. Given the pivotal role of Toll-like receptor 4 (TLR-4), a major innate immune sensor molecule, we hypothesized that genetic variations of TLR-4 may be associated to BD.
  
  
  METHODS
  Genomic DNAs from 572 BD patients and 202 healthy controls (HC) were analyzed for the distribution of six single nucleotides polymorphisms (SNPs) scattered along the TLR-4 locus (rs1927914, rs10759932, rs4986790, rs4986791, rs11536889 and rs11536891). Associations between BD and these polymorphisms were examined using the Chi-square test.
  
  
  RESULTS
  We found that rs1927914 AA and rs11536891 TT genotype are more frequent in BD patients than in controls (corrected p; pc=.02 and .02 respectively) particularly in early-onset BD patients (pc=.004 and .006) born during the summer season (pc=.02 and .002 respectively). We also found that rs4986790 AG and rs4986791 CT genotypes were significantly associated with presence of autoimmune thyroiditis (pc=.002).
  
  
  CONCLUSIONS
  Our results are to be confirmed by replication in independent BD cohorts.
  
  
  CONCLUSIONS
  We report for the first time a genetic association between BD and TLR-4 a major player of innate immunity. Possible mechanisms underlying bipolar disorders linking altered TLR-4 expression and increased susceptibility to infections and/or autoimmunity are discussed.
authors.affiliation: INSERM, UMRS 940, Hôpital Saint-Louis, Paris F75010, France; INSERM, U 955, IMRB, Psychiatrie Génétique, Créteil F94000, France; Fondation FondaMental, fondation de coopération scientifique, Créteil, France.
authors.forename: José
authors.initials: J
authors.lastname: Oliveira
authors.forename: Marc
authors.initials: M
authors.lastname: Busson
authors.forename: Bruno
authors.initials: B
authors.lastname: Etain
authors.forename: Stéphane
authors.initials: S
authors.lastname: Jamain
authors.forename: Nora
authors.initials: N
authors.lastname: Hamdani
authors.forename: Wahid
authors.initials: W
authors.lastname: Boukouaci
authors.forename: Kahina
authors.initials: K
authors.lastname: Amokrane
authors.forename: Mériem
authors.initials: M
authors.lastname: Bennabi
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Le Guen
authors.forename: Aroldo Ayub
authors.initials: AA
authors.lastname: Dargél
authors.forename: Josselin
authors.initials: J
authors.lastname: Houenou
authors.forename: Rayna
authors.initials: R
authors.lastname: Ivanova
authors.forename: Frank
authors.initials: F
authors.lastname: Bellivier
authors.forename: Chantal
authors.initials: C
authors.lastname: Henry
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Kahn
authors.forename: Dominique
authors.initials: D
authors.lastname: Charron
authors.forename: Rajagopal
authors.initials: R
authors.lastname: Krishnamoorthy
authors.forename: Laetitia
authors.initials: L
authors.lastname: Vervoitte
authors.forename: Marion
authors.initials: M
authors.lastname: Leboyer
authors.forename: Ryad
authors.initials: R
authors.lastname: Tamouza
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001714:Bipolar Disorder / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D051197:Toll-Like Receptor 4 / Q000235:genetics*; D055815:Young Adult
chemical_list: C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4
keywords: Bipolar disorders; Innate immunity; Polymorphism; TLR-4