AIF-1 gene does not confer susceptibility to Behçet’s disease: Analysis of extended haplotypes in Sardinian population

BACKGROUND: Behçet’s disease (BD) is a polygenic immune-mediated disorder characterized by a close association with the HLA-B*51 allele. The HLA region has a strong linkage disequilibrium (LD) and carries several genetic variants (e.g. MIC-A, TNF-α genes) identified as associated to BD because of their LD with HLA-B*51. In fact, the HLA-B*51 is inherited as part of extended HLA haplotypes which are well preserved in patients with BD. Sardinian population is highly differentiated from other Mediterranean populations because of a distinctive genetic structure with very highly preserved HLA haplotypes. PATIENTS AND METHODS: In order to identify other genes of susceptibility to BD within the HLA region we investigated the distribution of human Allograft Inflammatory Factor-1 (AIF-1) gene variants among BD patients and healthy controls from Sardinia. Six (rs2736182; rs2259571; rs2269475; rs2857597; rs13195276; rs4711274) AIF-1 single nucleotide polymorphisms (SNPs) and related extended haplotypes have been investigated as well as their LD within the HLA region and with HLA-B*51. Overall, 64 BD patients, 43 HLA-B*51 positive healthy controls (HC) and 70 random HC were enrolled in the study. RESULTS: HLA-B*51 was the only allele with significantly higher frequency (p(c) = 0.0021) in BD patients (40.6%) than in HC (9.8%). The rs2259571(T) AIF-1 variant had a significantly reduced phenotypic, but not allelic frequency in BD patients (72.1%; p(c) = 0.014) compared to healthy population (91.3%). That was likely due to the LD between HLA-B*51 and rs2259571(G) (p(c) = 9E-5), even though the rs2259571(G) distribution did not significantly differ between BD patients and HC. CONCLUSION: No significant difference in distribution of AIF-1 SNPs haplotypes was observed between BD patients and HC and between HLA-B*51 positive BD patients and HLA-B*51 positive HC. Taken together, these results suggest that AIF-1 gene is not associated with susceptibility to BD in Sardinia.