HLA and tumour necrosis factor (TNF) polymorphisms in ocular Behcet's disease

The role of HLA-B*51 and other major histocompatibility complex (MHC) genes in Behcet's disease (BD) remains unknown, We have performed HLA and tumour necrosis factor (TNF) polymorphism analysis in ED and evaluated their cont ribution to ocular disease, In this study, 102 patients and 115 controls of Middle Eastern descent were investigated by HLA and B*51 subtyping using n ovel primers, and by LT alpha NCo 1 and TNF -308 promoter polymorphism anal ysis. The frequency of the HLA-B*51 family of alleles was raised in patient s compared to controls (66% vs. 15%, P-c = 2.5x10(-12), OR = 10.9). The odd s ratio (OR) of this group of alleles for subgroups of patients was as foll ows: 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*5 108, 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 compa red to both non-ocular patients (P = 0.048, OR > 3.6) and to healthy contro ls (P = 0.022, OR > 4.3), The rare TNF-2 polymorphism at the TNF -308 promo ter position was associated with HLA-B*50 (not B*51), and was not associate d with ED. Thus, in this population the HLA*B51 family of alleles is a stro ng risk factor for BD, and in particular the development of ocular disease. HLA-B*51 subtyping did not define new markers for ED. A primary role for T NF gne polymorphisms in ED was not identified, but co-expression of the TNF B*B allele with HLA-B*51 may contribute to severity of ocular disease.