Association of haplotypes of the TLR8 locus with susceptibility to Crohn's and Behçet's diseases.
OBJECTIVE
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).


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Servicio de Inmunología, Unidad de Gestión Clínica "Intercentros de Laboratorios Clinicos", Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/ Universidad de Sevilla, Spain.
Lourdes
L
Ortiz-Fernández
Servicio de Inmunología, Unidad de Gestión Clínica "Intercentros de Laboratorios Clinicos", Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/ Universidad de Sevilla, Spain. jraul.garcia.sspa@juntadeandalucia.es.
José-Raúl
JR
García-Lozano
Servicio de Inmunología, Unidad de Gestión Clínica "Intercentros de Laboratorios Clinicos", Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/ Universidad de Sevilla, Spain.
Marco-Antonio
MA
Montes-Cano
Servicio de Inmunología, Unidad de Gestión Clínica "Intercentros de Laboratorios Clinicos", Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/ Universidad de Sevilla, Spain.
Marta
M
Conde-Jaldón
Unidad de Gestión Clínica "Enfermedades Digestivas", Hospital Universitario Virgen del Rocío, Sevilla, Spain.
Eduardo
E
Leo
Servicio de Medicina Interna, Hospital Clínico San Cecilio, Granada, Spain.
Norberto
N
Ortego-Centeno
Unidad de Enfermedad Inflamatoria Intestinal, Hospital Universitario Virgen de las Nieves, Granada, Spain.
María
M
Gómez-García
Servicio de Medicina Interna, Hospital Universitario Virgen del Rocío, Sevilla, Spain.
Francisco-José
FJ
García-Hernández
Unidad de Gestión Clínica "Enfermedades Digestivas", Hospital Universitario Virgen del Rocío, Sevilla, Spain.
José-Luis
JL
Márquez
Servicio de Enfermedades Autoinmunes, Hospital Clinic, Barcelona, Spain.
Gerard
G
Espinosa
Servicio de Reumatología, Complejo Hospitalario Universitario, A Coruña, Spain.
Genaro
G
Graña-Gil
Servicio de Reumatología, Hospital Universitario de Valme, Sevilla, Spain.
Juan
J
Sánchez-Bursón
Servei d´Inmunología. Hospital Universitari Son Espases, Palma de Mallorca, Spain.
María-Rosa
MR
Juliá
Servicio de Reumatología, Hospital Marqués de Valdecilla, Santander, Spain.
Ricardo
R
Blanco
Servicio de Medicina Interna, Hospital de Torrecárdenas, Almería, Spain.
Ana-Celia
AC
Barnosi-Marín
Servicio de Medicina Interna, Hospital Vall d´Hebron, Barcelona, Spain.
Roser
R
Solans
Servicio de Medicina Interna, Hospital Virgen del Camino, Pamplona, Spain.
Patricia
P
Fanlo
Servicio de Medicina Interna, Hospital Universitari Mútua, Terrassa, Spain.
Mónica
M
Rodríguez-Carballeira
Servicio de Medicina Interna, Hospital Universitario Carlos Haya, Málaga, Spain.
Teresa
T
Camps
Servicio de Reumatología, Hospital de la Princesa, Madrid, Spain.
Santos
S
Castañeda
Instituto de Parasitología y Biomedicina López Neyra, Consejo Superior de Investigaciones Científicas, Granada, Spain.
Javier
J
Martín
Servicio de Inmunología, Unidad de Gestión Clínica "Intercentros de Laboratorios Clinicos", Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/ Universidad de Sevilla, Spain.
María-Francisca
MF
González-Escribano
D000328:Adult; D001528:Behcet Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D003198:Computer Simulation; D003424:Crohn Disease / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D065840:Protective Factors; D018570:Risk Assessment; D012307:Risk Factors; D012737:Sex Factors; D013030:Spain; D051200:Toll-Like Receptor 8 / Q000235:genetics* / Q000276:immunology; D055815:Young Adult
C495349:TLR8 protein, human; D051200:Toll-Like Receptor 8