Polymorphism of Toll-like receptor 4 gene in bipolar disorder

Oliveira, J.; Busson, Marc; Étain, Bruno; Jamain, Stéphane; Hamdani, Nora; Boukouaci, Wahid; Amokrane, Kahina; Bennabi, Mériem; Guen, Emmanuel Le; Dargél, Aroldo A.; Houenou, Josselin; Ivanova, R.; Bellivier, Frank; Henry, Chantal; Kahn, Jean‐Pierre; Charron, Dominique; Krishnamoorthy, Rajagopal; Vervoitte, Laetitia; Leboyer, Marion; Tamouza, Ryad

doi:10.1016/j.jad.2013.09.043

Cited by 57 publications

(51 citation statements)

References 97 publications

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“…These patients were sampled from one large ongoing study that explored genetic and environmental risk factors of BD. Data regarding the association between TLR2/TLR4 genetic variations and BD have been previously published [22,23] and this was the same for the data regarding the association between AAO and childhood trauma [8]. To be included in this analysis, all cases had to have both a retrospective assessment of the AAO of BD, defined by the age of the first manic or depressive episode, as well as available genotypes for TLR2 or TLR4 genetic variations.…”

Section: Subjectsmentioning

confidence: 99%

“…Four functionally-relevant TLR2 and TLR4 single-nucleotide polymorphisms (SNPs) (rs4696480, rs3804099 and rs1927914, rs11536891 respectively) were selected based on previous genetic association studies of BD [22,23]. Genomic DNA was extracted from EDTA-treated peripheral blood samples or B-lymphoblastoid cell lines using the Nucleon BACC3 kit (GE HealthCare, Chalfont St Giles, UK).…”

Section: Tlr2 and Tlr4 Genetic Polymorphism Studiesmentioning

confidence: 99%

“…One of the proposed mechanisms is that acute stressor-mediated events may induce chronic alterations in immune/inflammatory processes in genetically predisposed individuals [12,13]. Exploring the control of innate immune responses in BD, we recently described associations between genetic variants of Toll-like receptor 2 (TLR2) and TLR4 loci and early-onset BD [22,23].…”

Section: Introductionmentioning

confidence: 99%

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Combined Effect of TLR2 Gene Polymorphism and Early Life Stress On the Age at Onset of Bipolar Disorders

Oliveira

Étain

Lajnef

et al. 2015

European Psychiatry

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Gene-environment interactions may play an important role in modulating the impact of earlylife stressful events on the clinical course of bipolar disorder (BD), particularly associated to early age at onset. Immune dysfunction is thought to be an important mechanism linking childhood trauma with early-onset BD, thus the genetic diversity of immune-related loci may account for an important part of the interindividual susceptibility to this severe subform. Here we investigated the potential interaction between genetic variants of Toll-like receptors 2 (TLR2) and 4 (TLR4), major innate immune response molecules to pathogens, and the childhood trauma questionnaire (CTQ) in age at onset of BD. We recruited 531 BD patients (type I and II or not otherwise specified), genotyped for the TLR2 rs4696480 and rs3804099 and TLR4 rs1927914 and rs11536891 single-nucleotide polymorphisms and recorded for history of childhood trauma using the CTQ. TLR2 and TLR4 risk genotype carrier state and history of childhood emotional, physical and sexual abuses were evaluated in relation to age at onset as defined by the age at first manic or depressive episode. We observed a combined effect of TLR2 rs3804099 TT genotype and reported sexual abuse on determining an earlier age at onset of BD by means of a Kaplan-Meier survival curve (p = 0.002; corrected p = 0.02). Regression analysis, however, was non-significant for the TLR2-CTQ sexual abuse interaction term. The negative effects of childhood sexual abuse on age at onset of BD may be amplified in TLR2 rs3804099 risk genotype carriers through immune-mediated pathways. Clinical characteristics of illness severity, immune phenotypes and history of early life infectious insults should be included in future studies involving large patient cohorts.

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Section: Subjectsmentioning

confidence: 99%

Section: Tlr2 and Tlr4 Genetic Polymorphism Studiesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Combined Effect of TLR2 Gene Polymorphism and Early Life Stress On the Age at Onset of Bipolar Disorders

Oliveira

Étain

Lajnef

et al. 2015

European Psychiatry

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“…[19][20][21][22] Although no genetic association studies include TLR4 in patietns with schizophrenia, an increased frequency of the TLR4 rs11536891 polymorphism was recently reported in patients with early-onset bipolar disorder compared with controls. 23 Several circumstances provide good reasons to study TLR4 in schizophrenia populations specifically. First, some studies indicate that TLR4 may play a significant role in neurodevelopment and plasticity.…”

Section: Introductionmentioning

confidence: 99%

Evidence of activation of the Toll-like receptor-4 proinflammatory pathway in patients with schizophrenia

García‐Bueno

Gassó

MacDowell

et al. 2016

jpn

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“…Several HLA genes and haplotypes are linked to autism [13], while HLA polymorphisms are amongst the most associated region in schizophrenia [20]. Furthermore, an association between bipolar patients with autoimmune comorbid disorders and genes encoding functional Toll Like Receptors (innate immunity) has been reported [21]. Strengthening the exploration of immunogenetic diversity in major psychiatric disorders, such as innate, adaptive immunity and inflammation pathways, is urgently needed as has been performed for cancer [22].…”

Section: Auto-immunity Early Infection and Immune-genetic Backgroundmentioning

confidence: 99%

Immuno-psychiatry: an agenda for clinical practice and innovative research

Leboyer

Berk

Yolken

et al. 2016

BMC Med

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BackgroundThe diagnostic scheme for psychiatric disorders is currently based purely on descriptive nomenclature given that biomarkers subtypes and clearly defined causal mechanisms are lacking for the vast majority of disorders. The emerging field of “immuno-psychiatry” has the potential to widen the exploration of a mechanism-based nosology, possibly leading to the discovery of more effective personalised treatment strategies.DiscussionDisturbances in immuno-inflammatory and related systems have been implicated in the aetiology, pathophysiology, phenomenology and comorbidity of several psychiatric disorders, including major mood disorders and schizophrenia. A fundamental challenge in their clinical management is to identify bio-signatures that might indicate risk, state, trait, prognosis or theragnosis. Here, we provide the rationale for a clinical and research agenda to refine future clinical practice and conceptual views, and to delineate pathways toward innovative treatment discovery.ConclusionThe development of bio-signatures will allow clinicians to tailor interventions to the abovementioned biomarker subtypes – a major translational goal for research in this field.

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Polymorphism of Toll-like receptor 4 gene in bipolar disorder

Cited by 57 publications

References 97 publications

Combined Effect of TLR2 Gene Polymorphism and Early Life Stress On the Age at Onset of Bipolar Disorders

Combined Effect of TLR2 Gene Polymorphism and Early Life Stress On the Age at Onset of Bipolar Disorders

Evidence of activation of the Toll-like receptor-4 proinflammatory pathway in patients with schizophrenia

Immuno-psychiatry: an agenda for clinical practice and innovative research

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