HLA-DRA Gene Polymorphisms Are Associated with Graves’ Disease as an Autoimmune Thyroid Disease

Abstract

Background. Autoimmune thyroid disease (AITD), one of the most prevalent organ-specific autoimmune diseases, mainly includes Graves’ disease (GD) and Hashimoto’s thyroiditis (HT). This study was aimed at researching the association between AITD and single nucleotide polymorphisms (SNPs) of the HLA-DRA gene. Methods. Using Hi-SNP high-throughput sequencing technology, we detected the distribution of three SNPs (rs3177928, rs7197, and rs3129878) of HLA-DRA genotypes in 1033 AITD patients (634 GD and 399 HT ones) and 791 healthy volunteers in Chinese Han Population. Chi-square test, multivariate logistic regression, and haplotype analysis were performed by SPSS and Haploview software to analyze the relationship between HLA-DRA gene polymorphisms and AITD. Results. The results show that allele frequency and genotype distribution of rs3177928 and rs7197 were correlated with AITD and GD compared with the healthy control group, but not with HT. Rs3177928 and rs7197 were correlated with AITD and HT in the allele model, dominant model, and overdominant model before and after gender and age adjustment, but not with HT. In addition, we found that two loci (rs3177928 and rs7197) constituted a linkage disequilibrium (LD) region, and haplotype AA was associated with AITD and GD. However, we found no association between rs3129878 and AITD. Conclusion. Our study is the first to find that rs3177928 and rs7197 of HLA-DRA are significantly correlated with AITD and GD in the Chinese Han population. This will help further reveal the pathogenesis of AITD and provide new candidate genes for the prediction or treatment of AITD.

Relationship between autoimmune thyroid antibodies and anti-nuclear antibodies in general patients

“…Researches based genetic material have become important evidences for elucidating the pathophysiological mechanisms of diseases. Found by studies that the SNPs rs3177928 and rs7197 were correlated with AITD and GD (compared with the healthy control group), but not with HT ( 32 ). The association of the SNP CD40 C/T-1 was evaluated in patients with AITD, and a significant association for CD40 C/T-1 polymorphism with GD was found, but not with HT.…”

Causal role of immune traits and inflammatory proteins in autoimmune thyroid disease: Mendelian randomization study

“…In our study, HLA DR expression on CD33 − HLA DR + in the myeloid cell panel was most prominently associated with increased AITD risk. Notably, the expression of HLA-DR indicates T cell activation, and cells expressing HLA-DR can serve as antigen-presenting cells, playing a crucial role in CD4 + T cellmediated autoimmune thyroiditis [31,32]. CD4 + T lymphocytes can be categorized into different subsets based on cellular differentiation and phenotype, namely Th1, Th2, Th17, and regulatory T cells (Treg) [33,34].…”

Molecular Mechanisms in Autoimmune Thyroid Disease

“…In another study, it was found that the SNPs rs3177928 and rs7197 were correlated with AITD and GBD (compared with the healthy control group), but not with HT. However, rs3177928 and rs7197 were correlated with AITD and HT in the allele model, dominant model, and overdominant model before and after gender and age adjustment, but not with HT [ 71 ].…”