The HLA association with Graves' disease is sex-specific in Hong Kong Chinese subjects

OBJECTIVE Graves' disease is associated with different HLA genes in Caucasians and the Chinese, in whom the HLA associations may be stronger in males than females. Common HLA-associated susceptibility in both races may occur at the HLA-DQ loci. The aims of this study were to examine the HLA-A, B, DR and DQ associations with Graves' disease in a Hong Kong Chinese population and to determine whether the HLA associations differ between the sexes and between subjects with and without thyrotoxic periodic paralysis. DESIGN HLA-A, B and DR types were determined by serological typing and DQA1 and DQB1 alleles by oligonucleotide probing of the respective enzymatically amplified gene. PATIENTS Ninety-seven Chinese patients with Graves' disease (31 males with, 35 males without and 31 females without thyrotoxic periodic paralysis) and 105 racially matched healthy controls. MEASUREMENTS Frequencies of HLA types/alleles at each locus were compared between patients and controls and between the Graves' subgroups using the χ² test. RESULTS HLA-B46, DR9 and DQB1*0303 were associated with Graves' disease in males only; these associations were weaker in males with thyrotoxic periodic paralysis. DR12, DQA1*0401 and DQB1*0301 were protective, regardless of sex or the presence of thyrotoxic periodic paralysis. The positive HLA associations in the Hong Kong Chinese were distinct from those in Caucasians whereas the protective haplotype was similar to that described in Caucasians. CONCLUSIONS These findings call in question the role of HLA genes in disease susceptibility but suggest a role for HLA in protection from Graves' disease.