Re-evaluation of heterogeneity in HLA-B*510101 associated with Behçet's disease

Area of Science:

• Immunogenetics
• Human genetics
• Molecular biology

Background:

• Behçet's disease (BD) is a chronic inflammatory disorder with unknown etiology.
• Association with human leukocyte antigen (HLA)-B51 or B*5101 is frequently reported.
• Previous studies indicated variations in B51 gene regions, but a comprehensive analysis was lacking.

Purpose of the Study:

• To fully sequence the HLA-B*5101 gene in diverse ethnic populations.
• To identify sequence variations in the HLA-B*5101 gene associated with Behçet's disease.
• To clarify the role of HLA-B*5101 and its flanking regions in BD pathogenesis.

Main Methods:

• Full gene sequencing of HLA-B*5101 from 37 individuals (Japanese, Turkish, Jordanian, Iranian patients and controls).
• Analysis of variations in the 5 eal-flanking region, exon, and intron.
• Identification and analysis of polymorphisms in the 3 eal-flanking region and haplotype construction.

Main Results:

• No variations were found in the 5 eal-flanking region, exon, or intron of HLA-B*510101 in any participants.
• Seven polymorphisms were identified in the 3 eal-flanking region of HLA-B*510101.
• Six shared haplotypes across ethnic groups were observed in the 3 eal-flanking region.

Conclusions:

• The susceptibility to Behçet's disease is conferred by the HLA-B*510101 gene itself.
• Genetic linkage disequilibrium with other genes is unlikely to be the cause of BD susceptibility.
• Phylogenetic analysis suggests conserved evolution of the HLA-B*510101 3 eal-flanking region, possibly due to unifying selection.