TY - JOUR
T1 - Polymorphism of Toll-like receptor 4 gene in bipolar disorder
AU - Oliveira, José
AU - Busson, Marc
AU - Etain, Bruno
AU - Jamain, Stéphane
AU - Hamdani, Nora
AU - Boukouaci, Wahid
AU - Amokrane, Kahina
AU - Bennabi, Mériem
AU - Le Guen, Emmanuel
AU - Dargél, Aroldo Ayub
AU - Houenou, Josselin
AU - Ivanova, Rayna
AU - Bellivier, Frank
AU - Henry, Chantal
AU - Kahn, Jean Pierre
AU - Charron, Dominique
AU - Krishnamoorthy, Rajagopal
AU - Vervoitte, Laetitia
AU - Leboyer, Marion
AU - Tamouza, Ryad
PY - 2014/1/1
Y1 - 2014/1/1
N2 - 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). Limitations 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.
AB - 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). Limitations 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.
KW - Bipolar disorders
KW - Innate immunity
KW - Polymorphism
KW - TLR-4
UR - http://www.scopus.com/inward/record.url?scp=84889086473&partnerID=8YFLogxK
U2 - 10.1016/j.jad.2013.09.043
DO - 10.1016/j.jad.2013.09.043
M3 - Article
C2 - 24176535
AN - SCOPUS:84889086473
SN - 0165-0327
VL - 152-154
SP - 395
EP - 402
JO - Journal of Affective Disorders
JF - Journal of Affective Disorders
IS - 1
ER -