Because particular
human leukocyte antigen (
HLA) DQ alleles are the major predisposing factors for
type 1 diabetes mellitus (
IDDM), we investigated whether they are shared by other endocrine
autoimmune diseases. We, therefore, analyzed the
HLA DQ genotypes of 171 patients with
IDDM, 271 with
Graves' disease (GD), 65 with Hashimoto's
thyroiditis, 51 with
postpartum thyroiditis, 53 with
Addison's disease (AD), and 271 healthy controls.
HLA DQA1 and DQB1 alleles were defined by polymerase chain reaction and sequence-specific
oligonucleotide hybridization as well as by single strand conformational polymorphism analysis.
HLA DQA1*0501 was significantly more frequent in
IDDM (60%), GD (65%), and
AD (70%) than in controls (43%); DQA1*0301 was significantly more frequent only in
IDDM (67% vs. 30% controls). The heterozygous state DQA1*0301/*0501 was found in 9% of controls and 35% of
IDDM (relative risk, 5.6). An
arginine at position 52 on either DQA1 allele was significantly more frequent in patients with
IDDM (94%), GD (80%), and AD (89%) compared with controls (66%).
HLA DQB1*0201 and DQB1*0302 were more frequent in
IDDM patients (*0201, 62% vs. 36% in controls, *0302, 59% vs. 19% controls), whereas DQB1*0602 was less frequent in
IDDM (4%) and GD (18% vs. 31% of controls). In conclusion, endocrine autoimmunity has a common immunogenetic background; susceptibility is conferred by DQA1*0501 as well as an
arginine at position 52 of DQA1 alleles, and protection against
IDDM and GD is conferred by DQB1*0602.