Logo

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

1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22

  1. 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.
  2. 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
  3. 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.
  4. 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.
  5. Unidad de Gestión Clínica “Enfermedades Digestivas”, Hospital Universitario Virgen del Rocío, Sevilla, Spain.
  6. Servicio de Medicina Interna, Hospital Clínico San Cecilio, Granada, Spain.
  7. Unidad de Enfermedad Inflamatoria Intestinal, Hospital Universitario Virgen de las Nieves, Granada, Spain.
  8. Servicio de Medicina Interna, Hospital Universitario Virgen del Rocío, Sevilla, Spain.
  9. Unidad de Gestión Clínica “Enfermedades Digestivas”, Hospital Universitario Virgen del Rocío, Sevilla, Spain.
  10. Servicio de Enfermedades Autoinmunes, Hospital Clinic, Barcelona, Spain.
  11. Servicio de Reumatología, Complejo Hospitalario Universitario, A Coruña, Spain.
  12. Servicio de Reumatología, Hospital Universitario de Valme, Sevilla, Spain.
  13. Servei d´Inmunología. Hospital Universitari Son Espases, Palma de Mallorca, Spain.
  14. Servicio de Reumatología, Hospital Marqués de Valdecilla, Santander, Spain.
  15. Servicio de Medicina Interna, Hospital de Torrecárdenas, Almería, Spain.
  16. Servicio de Medicina Interna, Hospital Vall d´Hebron, Barcelona, Spain.
  17. Servicio de Medicina Interna, Hospital Virgen del Camino, Pamplona, Spain.
  18. Servicio de Medicina Interna, Hospital Universitari Mútua, Terrassa, Spain.
  19. Servicio de Medicina Interna, Hospital Universitario Carlos Haya, Málaga, Spain.
  20. Servicio de Reumatología, Hospital de la Princesa, Madrid, Spain.
  21. Instituto de Parasitología y Biomedicina López Neyra, Consejo Superior de Investigaciones Científicas, Granada, Spain.
  22. 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.

CER8544 Submission on line
2015 Vol.33, N°6 ,Suppl.94 - PI 0117, PF 0122
Full Papers

Rheumatology Article

 

Abstract

OBJECTIVES:
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.

PMID: 26486764 [PubMed]

Received: 19/04/2015 - Accepted : 31/08/2015 - In Press: 19/10/2015 - Published: 04/11/2015