Actual Associations between HLA Haplotype and Graves' Disease Development

Area of Science:

• Immunogenetics
• Human Leukocyte Antigen (HLA) complex
• Autoimmune diseases

Background:

• The association between Human Leukocyte Antigen (HLA) genes and Graves' disease (GD) risk is well-established but often inconsistent, particularly in non-Asian populations.
• Previous studies have limitations in accurately identifying specific HLA alleles due to genotyping methods and population biases.

Purpose of the Study:

• To conduct high-resolution HLA genotyping in a Caucasian population using next-generation sequencing (NGS).
• To identify specific HLA alleles associated with Graves' disease (GD) morbidity and protective effects.
• To establish a reliable tool for personalized GD risk assessment based on HLA profiles.

Main Methods:

• Human Leukocyte Antigen (HLA) genotyping for loci -A, -B, -C, -DQB1, and -DRB1 was performed using next-generation sequencing (NGS).
• A cohort of 2376 individuals, comprising 159 Graves' disease patients and 2217 healthy controls, was analyzed.
• Statistical analysis was employed to determine significant associations between specific HLA alleles and GD risk.

Main Results:

• Significant associations were found between GD risk and several HLA alleles, including HLA-B*08:01, -B*39:06, -C*07:01, -DRB1*03:01, and -DQB1*03:01.
• Novel, independent GD-associated alleles with no linkage disequilibrium to known high-risk alleles were identified: HLA-B*39:06, -B*37:01, -C*14:02, -C*03:02, -C*17:01, and -DRB1*14:01.
• Protective associations were observed for alleles such as HLA-B*07:02, -C*07:02, -DRB1*07:01, and -DQB1*02:02, which were less frequent in GD patients.

Conclusions:

• Next-generation sequencing (NGS) provides precise HLA genotyping for accurate association studies in Graves' disease (GD).
• This study identified a novel set of HLA alleles that confer risk or protection against GD in Caucasians.
• The identified HLA alleles serve as a valuable tool for personalized risk assessment and potentially inform future therapeutic strategies for Graves' disease.