ASSOCIATION OF HLA-B51 AND LACK OF ASSOCIATION OF CLASS-II ALLELES WITH BEHCETS-DISEASE

Eighty-one Behcet's disease patients have been studied for HLA association by HLA-DRB1, -DQA1, -DQB1 and -DPB1 genotyping with the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique and for NcoI RFLP in the tumor-necrosis factor (TNF-beta) gene by Southern hybridization in addition to serological typing. In serological typing, the frequency of HLA-B51 was significantly increased in the patients. In PCR genotyping, there was a significant increase in the HLA-DRB1*0802, DQA1*0301 and DQB1*0303 alleles, whereas the frequencies of DRB1*1502, DQA1*0103, DQA1*0101, DQB1*0601 and DQB1*0501 showed a significant decrease in the patients. No significant difference was observed in any HLA-DPB1 alleles. Among them, B51 was found to be a genetic marker most strongly associated with Behcet's disease (p < 0.00005, chi-2 = 46.47, p(c)[corrected p] < 0.005). The positive and negative associations of class II alleles with the disease can be explained by linkage disequilibrium with B51, and do not reach statistical significance by the corrected p-value test. In NcoI RFLP typing in the TNF-beta gene, 250 kb centromeric of the HLA-B gene. the frequency of a 5.5 kb fragment was considerably decreased in the patients when compared to the controls, although the decrease was not statistically significant. These results indicate that the HLA class II genes or other non-HLA genes mapping within the class II region are not involved in the development of Behcet's disease but that HLA-B51 itself or a non-HLA gene located around the HLA-B gene region, more closely linked to HLA-B than the TNF-beta gene, does determine the genetic susceptibility to Behcet's disease.