TY - JOUR
T1 - Association between toll-like receptor 2 gene diversity and early-onset bipolar disorder
AU - Oliveira, José
AU - Hamdani, Nora
AU - Busson, Marc
AU - Etain, Bruno
AU - Bennabi, Meriem
AU - Amokrane, Kahina
AU - Boukouaci, Wahid
AU - Fortier, Catherine
AU - Marzais, François
AU - Bengoufa, Djaouida
AU - Bellivier, Frank
AU - Henry, Chantal
AU - Kahn, Jean Pierre
AU - Charron, Dominique
AU - Krishnamoorthy, Rajagopal
AU - Le Corvoisier, Philippe
AU - Leboyer, Marion
AU - Tamouza, Ryad
PY - 2014/8/20
Y1 - 2014/8/20
N2 - Background Toll-like receptor 2 (TLR2) molecules play a pivotal role in innate immune responses by their ability to recognize and sense a wide repertoire of infectious and endogenous cellular structural elements. Here we evaluated whether genetic variants in TLR2 influence the age of the disease onset in bipolar disorder (BD). Methods DNAs from 571 BD patients 229 early-onset (EO-BD) and 342 late-onset (LO-BD) and 199 healthy controls (HC) were analyzed for the following TLR2 polymorphisms: the 5′-UTR -196 to -174 insertion/deletion (ins/del), the intron 1 rs4696480 A/T, and the exon 3 rs3804099 C/T and rs3804100 C/T. PHASE software was used for haplotype reconstruction. Genetic associations were examined using a chi-square test. Results We found that the TLR2 rs3804099 TT was significantly more prevalent in EO-BD than in LO-BD patients (corrected p (pc)=0.024). After excluding family history of psychiatric disorders, we also found that the TLR2 rs4696480 TT genotype was significantly more prevalent in EO-BD as compared to LO-BD and controls (pc=0.002 and 0.002). Homozygous state for the insTTT haplotype, carrying the above mentioned risk genotypes, was significantly more frequent in EO-BD than in LO-BD patients (pc=0.007) and in EO-BD without family history of psychiatric disorders as compared to (i) those with positive history (pc=0.03), (ii) with LO-BD without family history (pc=0.001) and (iii) with HC (pc=0.009). Limitations Confirmation by replication in independent BD cohorts is warranted. Conclusions Our data suggest the potential role of TLR2 genetic variants in the pathogen-mediated susceptibility to BD.
AB - Background Toll-like receptor 2 (TLR2) molecules play a pivotal role in innate immune responses by their ability to recognize and sense a wide repertoire of infectious and endogenous cellular structural elements. Here we evaluated whether genetic variants in TLR2 influence the age of the disease onset in bipolar disorder (BD). Methods DNAs from 571 BD patients 229 early-onset (EO-BD) and 342 late-onset (LO-BD) and 199 healthy controls (HC) were analyzed for the following TLR2 polymorphisms: the 5′-UTR -196 to -174 insertion/deletion (ins/del), the intron 1 rs4696480 A/T, and the exon 3 rs3804099 C/T and rs3804100 C/T. PHASE software was used for haplotype reconstruction. Genetic associations were examined using a chi-square test. Results We found that the TLR2 rs3804099 TT was significantly more prevalent in EO-BD than in LO-BD patients (corrected p (pc)=0.024). After excluding family history of psychiatric disorders, we also found that the TLR2 rs4696480 TT genotype was significantly more prevalent in EO-BD as compared to LO-BD and controls (pc=0.002 and 0.002). Homozygous state for the insTTT haplotype, carrying the above mentioned risk genotypes, was significantly more frequent in EO-BD than in LO-BD patients (pc=0.007) and in EO-BD without family history of psychiatric disorders as compared to (i) those with positive history (pc=0.03), (ii) with LO-BD without family history (pc=0.001) and (iii) with HC (pc=0.009). Limitations Confirmation by replication in independent BD cohorts is warranted. Conclusions Our data suggest the potential role of TLR2 genetic variants in the pathogen-mediated susceptibility to BD.
KW - Bipolar disorder
KW - Early-onset
KW - Immunogenetics
KW - Innate immunity
KW - Toll like receptor 2
UR - http://www.scopus.com/inward/record.url?scp=84900852929&partnerID=8YFLogxK
U2 - 10.1016/j.jad.2014.04.059
DO - 10.1016/j.jad.2014.04.059
M3 - Article
C2 - 24882191
AN - SCOPUS:84900852929
SN - 0165-0327
VL - 165
SP - 135
EP - 141
JO - Journal of Affective Disorders
JF - Journal of Affective Disorders
ER -