HLA DQA1*0501 and DRB1*0301 antigens do not independently convey susceptibility to Graves' disease

Area of Science:

• Immunogenetics
• Endocrinology
• Human Genetics

Background:

• The human leukocyte antigen (HLA) complex is implicated in the genetic predisposition to Graves' disease.
• Specific HLA alleles, such as DQA1*0501 and DRB1*0301, are investigated for their role in Graves' disease susceptibility.

Purpose of the Study:

• To investigate the prevalence of HLA DQA1*0501 and DRB1*0301 antigens in Greek Graves' disease patients.
• To determine the association between these HLA antigens and clinical manifestations of Graves' disease, including thyroid eye disease (TED).
• To assess the combined effect of these HLA antigens on Graves' disease risk.

Main Methods:

• Genomic DNA was extracted from peripheral lymphocytes of 117 Graves' disease patients and 104 healthy controls.
• Polymerase chain reaction (PCR) amplification of HLA DQA1*0501 and DRB1*0301 regions.
• Hybridization with sequence-specific oligonucleotides (SSO) for HLA antigen characterization.

Main Results:

• Frequencies of both HLA DQA1*0501 and DRB1*0301 were significantly elevated in Graves' disease patients compared to controls (RR 4.2 and 4.5, respectively).
• Neither antigen independently predicted Graves' disease risk.
• The co-occurrence of both HLA DQA1*0501 and DRB1*0301 markedly increased the relative risk (RR) for Graves' disease, particularly in females (RR=27) versus males (RR=8.4).
• No association was found between these HLA antigens and a positive family history or the presence of TED.

Conclusions:

• HLA DQA1*0501 and DRB1*0301 are not independent risk factors for Graves' disease.
• The presence of both HLA DQA1*0501 and DRB1*0301 alleles significantly elevates the risk of developing Graves' disease in the Greek population, especially in females.
• These findings highlight the importance of combined HLA alleles in genetic susceptibility to autoimmune thyroid diseases.