Primary role of the HLA class II DRB1*0301 allele in Graves disease.

The association of the Graves disease (GD) with HLA DR3 and DQA10501 in Caucasians has been described previously. From these studies it could not be determined whether one specific locus was primarily involved. Using a case-control study design, we have examined the role of HLA class II gene polymorphisms in the predisposition for GD in a group of Belgian subjects. We demonstrated that both DRB10301 and DQA10501 alleles conferred significant susceptibility in the DRB10301-DQA10501 haplotype. The DRB10301 allele was the primary susceptibility allele for GD, however, because the susceptibility provided by DQA10501 was most likely due to it being in linkage disequilibrium with DRB10301. The DRB10701/x and DQA10201/x genotypes and the DRB10701-DQA10201 haplotype provided protection with an equal RR of 0.29. Predictive value calculations showed that testing for DRB1*0301 gave the highest positive predictive value for GD in females and males. This was, however, 10 times higher in females and predicted a 3.63% risk for a random female to develop GD.