L. Ortiz-Fernández1, J. García-Lozano2, M. Montes-Cano3, M. Conde-Jaldón4, E. Leo5, N. Ortego-Centeno6, M. Gómez-García7, F. García-Hernández8, J. Márquez9, G. Espinosa10, G. Graña-Gil11, J. Sánchez-Bursón12, M. Juliá13, R. Blanco14, A. Barnosi-Marín15, R. Solans16, P. Fanlo17, M. Rodríguez-Carballeira18, T. Camps19, S. Castañeda20, J. Martín21, M. González-Escribano22
2015 Vol.33, N°6 ,Suppl.94 - PI 0117, PF 0122
The aim of this study was to investigate the role of the TLR8, a mediator of innate inflammatory response, in susceptibility to two immune-mediated disorders characterised by dysregulation of the immune response, Crohn’s and Behçet’s diseases (CD and BD).
A total of 844 CD, 371 BD patients and 1385 controls were genotyped in 8 tag single nucleotide polymorphisms (tSNPs) in the locus TLR8 (chromosome X). All these tSNPs have a minor allele frequency greater than 0.05 in the Caucasian population.
The rs2407992 and the rs5744067 were associated with susceptibility to BD and CD, respectively (OR=1.34, 95%CI=1.10-1.62, p=0.0025 and OR=0.82, 95%CI=0.68-0.99, p=0.045, respectively). Although after stratification by gender, statistically significant differences in the distribution of the aforementioned SNPs were only observed in the females groups (BD OR=1.31, 95%CI=1.06-1.64, p=0.012 and CD OR=0.84, 95%CI=0.72-0.98, p=0.044) the trend was similar among males. Since the rs5744067 and rs2407992 are located in the same linkage disequilibrium block, we performed a haplotypic analysis by combination of the tSNPs. One haplotype (H1) was identified as a protective factor in BD (OR=0.75, 95%CI=0.62-0.90, p=0.0027) and another (H2) as a protective factor in CD (OR=0.78, 95%CI=0.64-094, p=0.0102). No statistically significant differences in the mean of the levels of expression attributable to the haplotype variants were found in the in silico analysis performed.
Our results suggest a relationship between the TLR8 and the susceptibility to CD and BD. Nevertheless, these differences could not be imputed to the levels of expression.
PMID: 26486764 [PubMed]
Received: 19/04/2015 - Accepted : 31/08/2015 - In Press: 19/10/2015 - Published: 04/11/2015