Study on association between polymorphism of HLA-DRB1 alleles and Behçet's disease.
ABSTRACT Behçet's disease (BD) is known to be associated with human leucocyte antigen (HLA)-B*51 in many ethnic groups. However, the association of HLA class II gene with BD has been described to be different according to different countries and regions.
This study aims to investigate the association between polymorphism of HLA-DRB1 alleles and BD.
Forty patients with BD and 100 healthy controls were typed for HLA-DRB1 alleles by the LABType SSO method.
The frequency of HLA-DRB1*14 was significantly higher in BD patients than in controls (P < 0.05), while the frequency of HLA-DRB1*15 was markedly lower in BD patients (P < 0.05). Regarding clinical manifestations, the frequency of HLA-DRB1*15 was significantly decreased in BD patients with genital ulcerations compared with controls (P < 0.05); the frequency of HLA-DRB1*14 was significantly increased in BD patients with erythema nodosum-like lesions and in BD patients with folliculitis-like lesions when compared to controls (P < 0.05, respectively). Moreover, the frequency of HLA-DRB1*14 was significantly increased in BD patients under 20 years of age at the onset of disease (P < 0.01), while the frequency of HLA-DRB1*15 was significantly decreased in them (P < 0.05), compared with controls.
The results suggested that HLA-DRB1 alleles might play an important role in the onset and clinical manifestations of BD.
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ABSTRACT: The distribution of the different HLA-B*51 suballeles among patients with Behçet’s disease (BD) of German (n=33) and Turkish (n=92) origin in comparison to their presence in the respective ethnically matched healthy control groups (German: n=325, Turkish: n=93) was studied. HLA-B*51x was significantly increased in both patient groups in comparison to the controls (Germans: 58% vs. 12%, OR 9.76, P<0.001; Turkish: 75% vs. 25%, OR 9.13, P<0.001). Molecular subtyping of B*51x revealed HLA-B*51011 and B*5108 as the predominant suballeles in both patient groups and controls although with a slightly increased frequency of HLA-B*5108 in the diseased individuals. HLA-B*5105 was the only further HLA-B*51x subtype detected in one Turkish patient heterozygous also for HLA-B*5101. HLA-B*5107 although present in a Turkish as well as German control was absent in the patient groups. There was also a tendency towards a higher degree of homozygosity for HLA-B*51x in both patient groups versus the matched controls (Germans: 10% in patients vs. 2,5% in controls; Turkish: 27% in patients vs. 13% in controls). Our study further supports previous hypothesis of an association of BD with B51 suballeles which share amino-acid residues at positions 63 and 67 as well as at positions 77–83 for specific peptide binding and natural killer (NK)-cell interactions. This applies to HLA-B*5101 and B*5108, but not to HLA-B*5107 different at position 67, which could be negatively associated with BD.Tissue Antigens 08/2001; 58(3):166 - 170. · 2.93 Impact Factor
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ABSTRACT: Behçet's disease (BD), also known as the Silk Road disease, is a blinding inflammatory disorder of young adults found predominantly between the Mediterranean basin and the Orient, and is strongly associated with the major histocompatibility complex (MHC) antigen HLA-B51. In this article we review the history of Behçet's disease since its first description by Hippocrates, the development of the trading routes collectively known as the Silk Road and the effect of population movement on the distribution of HLA-B51. The global distribution of this antigen among healthy control populations bears a striking similarity both to the ancient trading routes and the distribution of Behçet's disease, suggesting a genetic risk that migrated in parallel with population movement between the Mediterranean and Asia. However, certain indigenous Amerindian peoples have a high prevalence of HLA-B51 but no reported cases of BD. Furthermore, a clear genealogical relationship exists between eastern, but not central, Siberian populations with the Amerindians. Since a high level of recombination within the MHC is known to have occurred in these eastern populations before their migration into Beringia, we suggest that disruption of genetic loci in linkage disequilibria with HLA-B51 may be one reason for the absence of disease in these high HLA-B51-bearing populations. However, a contributory influence of environmental factors is not excluded by this data, and the wide variation that exists in relative risk of HLA-B51 even within Europe would support other non-genetic risk factors on the Silk Road which may be absent, or non-contributory to disease, in the Americas.Tissue Antigens 10/1999; 54(3):213-20. · 2.93 Impact Factor
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ABSTRACT: The role of HLA-B*51 and other major histocompatibility complex (MHC) genes in Behçet's disease (BD) remains unknown. We have performed HLA and tumour necrosis factor (TNF) polymorphism analysis in BD and evaluated their contribution to ocular disease. In this study, 102 patients and 115 controls of Middle Eastern descent were investigated by HLA and B*51 subtyping using novel primers, and by LT alpha NCo 1 and TNF 308 promoter polymorphism analysis. The frequency of the HLA-B*51 family of alleles was raised in patients compared to controls (66% vs. 15%, Pc=2.5x10(-12), OR=10.9). The odds ratio (OR) of this group of alleles for subgroups of patients was as follows: non-ocular patients 7.8, all ocular patients 12.6, blind patients >22. HLA-B*51 subtyping detected B*5101, 07, 08 and 09 alleles, with a similar frequency among patients and controls. HLA-Cw*1602 was associated with B*5108, but was not an independent risk factor for disease. The LT alpha (TNFB*2) allele was associated with HLA-B*51 among patients and the frequency of this allele was significantly higher among completely blind patients compared to both non-ocular patients (P=0.048, OR >3.6) and to healthy controls (P=0.022, OR >4.3). The rare TNF-2 polymorphism at the TNF -308 promoter position was associated with HLA-B*50 (not B*51), and was not associated with BD. Thus, in this population the HLA*B51 family of alleles is a strong risk factor for BD, and in particular the development of ocular disease. HLA-B*51 subtyping did not define new markers for BD. A primary role for TNF gne polymorphisms in BD was not identified, but co-expression of the TNFB*2 allele with HLA-B*51 may contribute to severity of ocular disease.Tissue Antigens 10/1999; 54(3):264-72. · 2.93 Impact Factor