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The HLA association with Graves' disease is sex-specific in Hong Kong Chinese subjects
D A Cavan1, M A Penny, K H Jacobs
1Department of Medicine, University of Birmingham, UK.
Insights
Human Leukocyte Antigen (HLA) genes show varied associations with Graves' disease in Chinese males, with some alleles offering protection. These findings suggest HLA plays a protective role rather than a susceptibility role in Graves' disease.
Area of Science:
- Immunogenetics
- Endocrinology
Background:
- Graves' disease (GD) exhibits differing Human Leukocyte Antigen (HLA) associations across ethnic groups, with potential sex-based variations.
- Previous studies suggest HLA-DQ loci may be involved in GD susceptibility in both Caucasians and Chinese populations.
Purpose of the Study:
- To investigate HLA-A, B, DR, and DQ associations with Graves' disease in Hong Kong Chinese.
- To determine if these HLA associations differ between sexes and in patients with thyrotoxic periodic paralysis (TPP).
Main Methods:
- Serological typing for HLA-A, B, DR; oligonucleotide probing for DQA1 and DQB1 alleles.
- Comparison of HLA type/allele frequencies between 97 Chinese GD patients and 105 controls using chi-squared test.
Main Results:
- HLA-B46, DR9, and DQB1*0303 were associated with GD in males only, with weaker links in males with TPP.
- DR12, DQA1*0401, and DQB1*0301 demonstrated a protective effect against GD, independent of sex or TPP.
- Positive HLA associations in Hong Kong Chinese differed from Caucasian findings, while protective haplotypes showed similarity.
Conclusions:
- The study questions the role of HLA genes in GD susceptibility.
- Findings suggest a significant role for specific HLA alleles in providing protection against Graves' disease.
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 chi 2-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.