HLA DQA1X0501 and DRB1*0301 antigens do not independently convey susceptibility to Graves' disease

Genes of, or closely associated to, the HLA complex are assumed to contribu te to the genetic predisposition of Graves' disease. The aim of this study was to investigate the presence of the HLA DQA1*0501 and DRB1*0301 antigens in Greek patients with Graves' disease. In addition, we tried to establish if there is any association between these antigens and any of the clinical manifestations of the disease. We examined 117 patients with Graves' disea se and 104 healthy controls. DNA was extracted from peripheral lymphocytes and the HLA DQA1*0501 and DRB1*0301 genomic regions were amplified by PCR a nd characterized by hybridization with sequence specific oligonucleotides ( SSO). Two of the patients had a positive family history for Graves' disease and 46 had clinical thyroid eye disease (TED). The frequencies of both DQA 1*0501 and DRB1*0301 anti-gens were significantly increased in patients com pared to controls (relative risk [RR] 4.2 and 4.5 for each antigen respecti vely), Neither of these two antigens was an independent risk factor for Gra ves' disease. However, the combination of both these HLA antigens resulted in a striking increase in the RR for development of Graves' disease especia lly in females (RR/F-27, RR/M=8.4). No association was found between these antigens and positive family history or the presence of TED. These data sug gest that HLA DQA1*0501 and DRB1*0301 antigens are not independent risk fac tors for the development of Graves' disease. On the contrary, the presence of both these alleles results in a significant increase in the RR for the d evelopment of Graves' disease in the Greek population, particularly in fema les. (C)2001, Editrice Kurtis.