Toxoplasma gondii exposure may modulate the influence of TLR2 genetic variation on bipolar disorder: a gene–environment interaction study

José Oliveira, Rémi Kazma, Edith Le Floch, Meriem Bennabi, Nora Hamdani, Djaouida Bengoufa, Mehdi Dahoun, Céline Manier, Frank Bellivier, Rajagopal Krishnamoorthy, Jean François Deleuze, Robert H Yolken, Marion Leboyer, Ryad Tamouza

Research output: Contribution to journalArticle

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 TLR2rs3804099 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.

Original languageEnglish (US)
Article number11
JournalInternational Journal of Bipolar Disorders
Volume4
Issue number1
DOIs
StatePublished - Dec 1 2016

Fingerprint

Toxoplasma
Bipolar Disorder
Single Nucleotide Polymorphism
Pattern Recognition Receptors
Immunogenetics
Human Herpesvirus 2
Seroepidemiologic Studies
Human Herpesvirus 1
Sample Size
Genes
Regression Analysis

Keywords

  • Bipolar disorder
  • Genetic diversity
  • Gene–environment interaction
  • Infection
  • Innate immunity
  • Pathogen recognition receptor

ASJC Scopus subject areas

  • Biological Psychiatry
  • Psychiatry and Mental health

Cite this

Toxoplasma gondii exposure may modulate the influence of TLR2 genetic variation on bipolar disorder : a gene–environment interaction study. / Oliveira, José; Kazma, Rémi; Le Floch, Edith; Bennabi, Meriem; Hamdani, Nora; Bengoufa, Djaouida; Dahoun, Mehdi; Manier, Céline; Bellivier, Frank; Krishnamoorthy, Rajagopal; Deleuze, Jean François; Yolken, Robert H; Leboyer, Marion; Tamouza, Ryad.

In: International Journal of Bipolar Disorders, Vol. 4, No. 1, 11, 01.12.2016.

Research output: Contribution to journalArticle

Oliveira, J, Kazma, R, Le Floch, E, Bennabi, M, Hamdani, N, Bengoufa, D, Dahoun, M, Manier, C, Bellivier, F, Krishnamoorthy, R, Deleuze, JF, Yolken, RH, Leboyer, M & Tamouza, R 2016, 'Toxoplasma gondii exposure may modulate the influence of TLR2 genetic variation on bipolar disorder: a gene–environment interaction study', International Journal of Bipolar Disorders, vol. 4, no. 1, 11. https://doi.org/10.1186/s40345-016-0052-6
Oliveira, José ; Kazma, Rémi ; Le Floch, Edith ; Bennabi, Meriem ; Hamdani, Nora ; Bengoufa, Djaouida ; Dahoun, Mehdi ; Manier, Céline ; Bellivier, Frank ; Krishnamoorthy, Rajagopal ; Deleuze, Jean François ; Yolken, Robert H ; Leboyer, Marion ; Tamouza, Ryad. / Toxoplasma gondii exposure may modulate the influence of TLR2 genetic variation on bipolar disorder : a gene–environment interaction study. In: International Journal of Bipolar Disorders. 2016 ; Vol. 4, No. 1.
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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 TLR2rs3804099 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.",
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T2 - a gene–environment interaction study

AU - Oliveira, José

AU - Kazma, Rémi

AU - Le Floch, Edith

AU - Bennabi, Meriem

AU - Hamdani, Nora

AU - Bengoufa, Djaouida

AU - Dahoun, Mehdi

AU - Manier, Céline

AU - Bellivier, Frank

AU - Krishnamoorthy, Rajagopal

AU - Deleuze, Jean François

AU - Yolken, Robert H

AU - Leboyer, Marion

AU - Tamouza, Ryad

PY - 2016/12/1

Y1 - 2016/12/1

N2 - 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 TLR2rs3804099 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.

AB - 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 TLR2rs3804099 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.

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KW - Genetic diversity

KW - Gene–environment interaction

KW - Infection

KW - Innate immunity

KW - Pathogen recognition receptor

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