title: The absence of disease-specific polymorphisms within the HLA-B51 gene that is the susceptible locus for Behçet's disease.
abstract: Behçet's disease is known to be associated with HLA-B51 in many different populations. Genetic evidence supports that the susceptible gene for Behçet's disease is the HLA-B51 allele at the HLA-B locus. This study was aimed to determine the HLA-B51 nucleotide sequence variation in three Behçet's disease patients and three healthy controls in order to elucidate if any disease specific mutations or polymorphisms may exist in the HLA-B51 gene of patients. Long-range polymerase chain reaction (PCR) was first carried out to give a PCR-amplified product of 9.5 kb which was then used as a template for nested PCR to give a final amplified product of 4.2 kb. This final product containing the 1.3-kb promoter/enhancer region and the entire HLA-B gene except for a 363-bp 3' terminal end segment encoding the 3' untranslated region was subcloned by the BP cloning technique and sequenced. The sequencing results showed that all the patients possessed the HLA-B*51011 allele, and there were no differences in the exonic nucleotide sequences between the three Behçet's disease patients and the three healthy controls. The HLA-B*51011 intronic and promoter/enhancer nucleotide sequences from the three patients had 22 single nucleotide polymorphisms (SNPs), a single insertion of 6 bp and a single deletion of 2 bp. On the other hand, the three healthy controls had 24 SNPs in their intronic and promoter/enhancer regions. However, none of these polymorphisms in the patients were specific for the disease. Therefore, these results clearly demonstrate that the HLA-B exonic sequence that encodes the HLA-B51 allele is the real pathogenic factor in Behçet's disease.
authors.affiliation: Department of Genetic Information, Division of Molecular Life Science, Tokai University School of Medicine, Bohseidai, Isehara, Kanagawa, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Sano
authors.forename: K
authors.initials: K
authors.lastname: Yabuki
authors.forename: Y
authors.initials: Y
authors.lastname: Imagawa
authors.forename: T
authors.initials: T
authors.lastname: Shiina
authors.forename: N
authors.initials: N
authors.lastname: Mizuki
authors.forename: S
authors.initials: S
authors.lastname: Ohno
authors.forename: J K
authors.initials: JK
authors.lastname: Kulski
authors.forename: H
authors.initials: H
authors.lastname: Inoko
mesh_terms: D024506:5' Flanking Region / Q000235:genetics; D001528:Behcet Syndrome / Q000235:genetics* / Q000276:immunology*; D004742:Enhancer Elements, Genetic / Q000235:genetics; D005091:Exons; D020022:Genetic Predisposition to Disease; D015235:HLA-B Antigens / Q000235:genetics*; D059949:HLA-B51 Antigen; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D017422:Sequence Analysis, DNA
chemical_list: D015235:HLA-B Antigens; D059949:HLA-B51 Antigen