HLA class II DNA genotypes in Graves' disease: clues to inheritance of the HLA-linked component of susceptibility.

Restriction fragment length polymorphism analysis using DQ alpha, DQ beta and DR beta cDNA probes was performed in Graves' disease patients and control subjects. The following restriction fragment patterns were increased in frequency in patients compared with control subjects: 10 + 7.0 + 4.0kb DR beta/TaqI fragments (66% vs 32%; P less than 0.01; corrected P less than 0.06), 7.0 + 4.0kb DQ beta/BamHI fragments (55% vs 15%; P less than 0.001; corrected P less than 0.006), and a DQ alpha/TaqI 4.6kb fragment (75% vs 36%; P less than 0.005; corrected P less than 0.02). These associations could be accounted for by the known association of the B8-DR3 haplotype with the disorder. No non-DR3-related restriction fragment pattern was associated with the disease using any of the probes with restriction enzymes TaqI and BamHI. The 10 + 7.0 + 4.0kb DR beta/TaqI restriction pattern was identified in 23 of 35 Graves' disease patients. All 23 subjects were heterozygous for this pattern. This was inconsistent with simple recessive inheritance of the DR3-associated component of disease susceptibility (P = 0.01). The implications of these findings are discussed with reference to models for the inheritance of the HLA-linked component of Graves' disease susceptibility.