title: Toxoplasma gondii exposure may modulate the influence of TLR2 genetic variation on bipolar disorder: a gene-environment interaction study.
abstract: BACKGROUND
  Genetic vulnerability to environmental stressors is yet to be clarified in bipolar disorder (BD), a complex multisystem disorder in which immune dysfunction and infectious insults seem to play a major role in the pathophysiology. Association between pattern-recognition receptor coding genes and BD had been previously reported. However, potential interactions with history of pathogen exposure are yet to be explored.
  
  
  METHODS
  138 BD patients and 167 healthy controls were tested for serostatus of Toxoplasma gondii, CMV, HSV-1 and HSV-2 and genotyped for TLR2 (rs4696480 and rs3804099), TLR4 (rs1927914 and rs11536891) and NOD2 (rs2066842) polymorphisms (SNPs). Both the pathogen-specific seroprevalence and the TLR/NOD2 genetic profiles were compared between patients and controls followed by modelling of interactions between these genes and environmental infectious factors in a regression analysis.
  
  
  RESULTS
  First, here again we observed an association between BD and Toxoplasma gondii (p = 0.045; OR = 1.77; 95 % CI 1.01-3.10) extending the previously published data on a cohort of a relatively small number of patients (also included in the present sample). Second, we found a trend for an interaction between the TLR2 rs3804099 SNP and Toxoplasma gondii seropositivity in conferring BD risk (p = 0.017, uncorrected).
  
  
  CONCLUSIONS
  Pathogen exposure may modulate the influence of the immunogenetic background on BD. A much larger sample size and information on period of pathogen exposure are needed in future gene-environment interaction studies.
authors.affiliation: INSERM, U1160, Hôpital Saint Louis, Paris, France.|Fondation FondaMental, Créteil, France.
authors.forename: José
authors.initials: J
authors.lastname: Oliveira
authors.affiliation: Centre National de Génotypage, CEA, Evry, France.
authors.forename: Rémi
authors.initials: R
authors.lastname: Kazma
authors.affiliation: Centre National de Génotypage, CEA, Evry, France.
authors.forename: Edith
authors.initials: E
authors.lastname: Le Floch
authors.affiliation: INSERM, U1160, Hôpital Saint Louis, Paris, France.|Fondation FondaMental, Créteil, France.
authors.forename: Meriem
authors.initials: M
authors.lastname: Bennabi
authors.affiliation: Fondation FondaMental, Créteil, France.|Faculté de Médecine, Université Paris-Est, Créteil, France.|AP-HP, DHU PePSY, Pôle de Psychiatrie, Hôpitaux Universitaires Henri Mondor, Créteil, France.|INSERM, U955, Psychiatrie Translationnelle, Créteil, France.
authors.forename: Nora
authors.initials: N
authors.lastname: Hamdani
authors.affiliation: Laboratoire Jean Dausset and LabEx Transplantex, Hôpital Saint Louis, Paris, France.
authors.forename: Djaouida
authors.initials: D
authors.lastname: Bengoufa
authors.affiliation: Laboratoire Jean Dausset and LabEx Transplantex, Hôpital Saint Louis, Paris, France.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Dahoun
authors.affiliation: INSERM, U1160, Hôpital Saint Louis, Paris, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Manier
authors.affiliation: Sorbonne Paris-Cité, Université Paris Diderot, Paris, France.|INSERM UMR-S1144-VariaPsy, Hôpital Fernand Widal, Paris, France.
authors.forename: Frank
authors.initials: F
authors.lastname: Bellivier
authors.affiliation: INSERM, U1160, Hôpital Saint Louis, Paris, France.
authors.forename: Rajagopal
authors.initials: R
authors.lastname: Krishnamoorthy
authors.affiliation: Centre National de Génotypage, CEA, Evry, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Deleuze
authors.affiliation: Stanley Laboratory of Developmental Neurovirology, Johns Hopkins University Medical Center, Baltimore, USA.|Stanley Research Program, Sheppard Pratt, Baltimore, MD, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Yolken
authors.affiliation: Fondation FondaMental, Créteil, France.|Faculté de Médecine, Université Paris-Est, Créteil, France.|AP-HP, DHU PePSY, Pôle de Psychiatrie, Hôpitaux Universitaires Henri Mondor, Créteil, France.|INSERM, U955, Psychiatrie Translationnelle, Créteil, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Leboyer
authors.affiliation: INSERM, U1160, Hôpital Saint Louis, Paris, France. tamouza.ryad@gmail.com.|Fondation FondaMental, Créteil, France. tamouza.ryad@gmail.com.|Laboratoire Jean Dausset and LabEx Transplantex, Hôpital Saint Louis, Paris, France. tamouza.ryad@gmail.com.|Sorbonne Paris-Cité, Université Paris Diderot, Paris, France. tamouza.ryad@gmail.com.
authors.forename: Ryad
authors.initials: R
authors.lastname: Tamouza
keywords: Bipolar disorder; Genetic diversity; Gene–environment interaction; Infection; Innate immunity; Pathogen recognition receptor