Genetics of Behcet disease inside and outside the MHC
| Autor: | Seiamak Bahram, Nobuhisa Mizuki, Ryoji Yamakawa, Akira Meguro, Akira Oka, Shigeaki Ohno, Yoshihiko Katsuyama, Masao Ota, Takenosuke Yuasa, Toshihiko Fujioka, Eiichi Okada, Hidetoshi Inoko |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Linkage disequilibrium
Genotype Immunology Genome-wide association study Locus (genetics) Human leukocyte antigen Linkage Disequilibrium General Biochemistry Genetics and Molecular Biology Gene Frequency Rheumatology Genetic predisposition HLA-B Antigens Humans Immunology and Allergy Medicine Genetic Predisposition to Disease Allele Genetics HLA-A Antigens business.industry Behcet Syndrome Histocompatibility Testing Haplotype Phenotype Haplotypes Case-Control Studies business Genome-Wide Association Study Microsatellite Repeats |
| Zdroj: | Annals of the Rheumatic Diseases. 69:747-754 |
| ISSN: | 0003-4967 |
| DOI: | 10.1136/ard.2009.108571 |
| Popis: | Background Behcet disease (BD) is a rare, chronic, systemic, inflammatory disorder characterised by recurrent ocular, genital and skin lesions. Although its aetiology is still uncertain, an intricate interplay between the environment (eg, viruses) and the host seems to initiate and/or perpetuate the disease, although the mechanism remains speculative. Since the identification of HLA-B*5101 (and more recently of MICA ) as a susceptibility locus for BD, the identification of additional genetic locus/loci, whether inside, or perhaps more importantly outside the MHC has clearly stalled. Objective To carry out a genome-wide association study (GWAS) of BD. Methods 300 Japanese patients with BD and an equal number of controls were recruited. The samples were screened using a dense panel of 23 465 microsatellites (MS) covering the entire genome. Results The six best (of a total of 147) positively associated MS with BD were identified. Of these six, two were located within the human leucocyte antigen (HLA) class I region itself. Although one of these was clearly reminiscent of the association with HLA-B , the second, not in linkage disequilibrium with the former, was in the telomeric side of the class I region and remained to be formally identified. HLA genotyping and haplotype analysis conclusively led to the deciphering of a dual, independent, contribution of two HLA alleles to the pathogenesis of BD: HLA-B*5101 and HLA-A*26 . Conclusions This GWAS highlights the premier genetic susceptibility locus for BD as the major histocompatibility complex itself, wherein reside two independent loci: HLA-B and HLA-A . |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|