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

Abstract

BackgroundBehçet’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 methodsIn 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.ResultsHLA-B*51 was the only allele with significantly higher frequency (pc = 0.0021) in BD patients (40.6%) than in HC (9.8%). The rs2259571T AIF-1 variant had a significantly reduced phenotypic, but not allelic frequency in BD patients (72.1%; pc = 0.014) compared to healthy population (91.3%). That was likely due to the LD between HLA-B*51 and rs2259571G (pc = 9E-5), even though the rs2259571G distribution did not significantly differ between BD patients and HC.ConclusionNo 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.

Development and validation of a Behçet's Disease Damage Index for adults with BD: An Explicit, Composite and Rated (ECR) tool

“…The BODI study was conducted on 228 patients from 10 southern European centers with a male : female ratio of 0.97:1. Moreover, a recent study from Cagliari, Italy reported a male : female ratio of 0.5:1, 20 while in this study the male : female ratio was 2.6:1. Furthermore, a possible cultural reluctance among women from Eastern countries to visit a physician for genital ulcers leading to delayed diagnosis of BD with the development of more severe organ involvement may partly serve as another cause.…”

Prevalence of antiphospholipid antibodies in Behçet's disease: A systematic review and meta-analysis

“…In absence of universally accepted diagnostic laboratory test, the diagnosis can only be made based on clinical symptoms and signs [1][2][3]. Patients with BD share some common features with autoimmune and autoinflammatory diseases [4][5][6][7][8]. The prevalence of BD is higher in the ancient silk route areas-geographically the Mediterranean and the Middle East regions (between the latitudes of 30˚N and 45˚N) [9,10] with an estimated worldwide prevalence of 10.3/100,000 and is equally distributed in men and women [11,12].…”

<p>Assessment Of Circulating Endothelial Cells And Their Progenitors As Potential Biomarkers Of Disease Activity And Damage Accrual In Behçet’s Syndrome</p>

“…The etiology of BS remains unknown, although the most widely held pathogenic hypothesis is that of aberrant autoinflammatory response triggered by an environmental agent in genetically susceptible subjects 2,3. Supporting this is the geoepidemiology of the disease and the association with polymorphisms in the HLA complex, particularly the HLA-B*51 4–6…”