CARD15 polymorphisms in Behçet's disease.
Ahmad T., Zhang L., Gogus F., Verity D., Wallace G., Madanat W., Fayyad F., James T., Neville M., Kanawati C., Fortune F., Celik A., Stanford M., Jewell DP., Marshall SE.
BACKGROUND: Behçet's disease (BD) is a chronic multi-system inflammatory disorder of unknown aetiology, which shares many features of the inflammatory bowel diseases (IBDs). CARD15 has recently been identified as the first susceptibility gene in Crohn's disease (CD). OBJECTIVE: Given certain clinical and pathological similarities between CD and BD, and recent evidence of linkage of BD to the CARD15 genomic region, the aim of this study was to investigate the role of CARD15 variants in determining susceptibility to BD. METHODS: We studied 374 BD patients from three ethnically homogeneous cohorts (white English, Turkish, and Middle Eastern Arabs of Palestinian and Jordanian descent). Mutation detection of CARD15 was performed by direct sequencing in a subset of patients from each group and the identified variants were genotyped in the complete cohorts. Case-control analyses were carried out with additional stratification by the BD-associated allele, HLA-B*51. RESULTS: Mutation detection identified six previously described CARD15 polymorphisms at a frequency of > 3%. Additionally, two of the three CD-associated polymorphisms were present, but at low frequency. The frequency of haplotypes, constructed from nine genotyped polymorphisms, demonstrated significant variation between different ethnic groups. However, case-control analyses demonstrated no association between the CARD15 polymorphisms and susceptibility to BD, irrespective of HLA-B*51 status. CONCLUSION: CARD15 variant alleles are not associated with susceptibility to BD. Other shared loci, currently under investigation, may determine susceptibility to both CD and BD.