Presentation: Association of Killer Immunoglobulin-like Receptor Gene 3DL1/3DS1 Polymorphism with Behcet’s Disease is Stronger in Male Patients (2007)

843 Association of Killer Immunoglobulin-like Receptor Gene 3DL1/3DS1 Polymorphism with Behcet’s Disease is Stronger in Male Patients

PURPOSE. Behçet’s disease (BD) has strongly been associated with HLA-B51, but its pathogenic significance has yet to be identified. Bw4 epitope of HLA-B molecules can bind to a group of highly polymorphic receptors expressed on natural killer (NK) cells and cytotoxic T cells, which are known as killer immunoglobulin-like receptor (KIR) family. Epistatic interaction of HLA-Bw4 epitopes and KIR3DS1 has been suggested as having a protective role in the progression of HIV1 infection or influencing the development of psoriatic arthritis. We aimed to analyse the role of KIR3DL1/DS1 polymorphism and its interaction with the respective HLA ligands, -B51 molecules, in the pathogenesis of BD.
METHODS. A group of 241 patients with BD and 235 healthy controls compromised the study group. All individuals were genotyped for the KIR3DL1/DS1 polymorphism. Phenotype frequencies were compared using a chi-square test, and the interaction of 3DL1/DS1 polymorphism with their respective ligands HLA-Bw4 or -B51 has been tested.
RESULTS. The overall distribution of KIR3DS1 and KIR3DL1 genotypes were found to be significantly different between Bw4-positive BD patients and Bw4-positive healthy controls (χ2 for trend, P = 0.019). In ligand positive individuals, homozygous 3DL1 genotype was associated with 1.7-times increased the risk for BD (95% CI 1.1-2.6, P = 0.013). Association of 3DL1/3DL1 genotype with BD was also significant in the comparison of Bw4-positive but HLA-B51 negative patients and controls (OR=2.1, 95% CI 1.2-3.6, P=0.007). The associations between BD and 3DL1/3DL1, Bw4 with 3DL1/3DL1, Bw4-Isoleucin 80 with 3DL1/3DL1, and B51 with 3DL1/3DL1 were much stronger in male BD patients compared to the female patients (OR 2.0 vs 0.9; 3.1 vs 1.6; 3.6 vs 1.7; 4.9 vs 2.3, respectively).
CONCLUSIONS. Selective increase of 3DL1/3DL1 genotype in the ligand positive individuals suggest that interaction of Bw4 epitopes with KIR3DL1 molecules may have a role in the pathogenesis of BD, and it may be one of the pathogenic mechanisms of HLA-B51 association. A more prominent association of KIR3DL1/DS1 polymorphism with BD in male patients compared to females needs further investigation, which may provide further insights in understanding the more severe disease course in male patients.

 J. Duymaz Tozkir, None; F. Uyar, None; G. Saruhan Direskeneli, None; A. Gul, None.