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  • Title: Re-evaluation of heterogeneity in HLA-B*510101 associated with Behçet's disease.
    Author: Takemoto Y, Naruse T, Namba K, Kitaichi N, Ota M, Shindo Y, Mizuki N, Gul A, Madanat W, Chams H, Davatchi F, Inoko H, Ohno S, Kimura A.
    Journal: Tissue Antigens; 2008 Oct; 72(4):347-53. PubMed ID: 18700875.
    Abstract:
    Behçet's disease (BD) is a chronic inflammatory disease characterized by oral aphthous ulcers, genital ulcers, uveitis and skin lesions. Etiology and pathogenesis of BD are not fully elucidated, but the association with human leukocyte antigen (HLA)-B51 or B*5101 has been repeatedly reported. Previous studies have shown that there are few sequence variations in the protein-coding region of B51, while there is a report on many variations in the 5'-flanking region and intron. In this study, HLA-B*5101 gene from 37 individuals including Japanese, Turkish, Jordanian and Iranian patients and healthy controls were fully sequenced to further clarify the B*5101 gene in association with BD. We found that all the patients and healthy controls carried B*510101 with no variation in the 5'-flanking region, exon and intron. However, seven polymorphisms were found in the 3'-flanking region. These polymorphisms composed of six haplotypes that were shared and stretched over the ethnic groups, suggesting that the susceptibility to BD was conferred by the B*510101 itself and not by any genes in linkage disequilibrium with B*510101. In addition, phylogenetic analyses of B*510101 showed that the 3'-flanking sequences followed an evolutional divergence differently from that of the other regions, implying that a unifying selection might operate to conserve B*510101.
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