Abstract
Autoimmune thyroid diseases (AITDs), including Graves’ disease (GD) and Hashimoto’s thyroiditis (HT), are among the commonest autoimmune disorders, affecting approximately 2% - 5% of the population. Epidemiological data support strong genetic influences on the development of AITD. The identification of genes placing individuals at an increased risk for the development of AITD has been a slow process. However, over the last 20 years or so real progress has been made with the mapping of novel loci, via a number of different approaches. The first AITD gene discovered, Human Leucocyte Antigen (HLA)/Major Histocompatibility Complex (MHC), is associated with both GD and HT. Non-MHC genes that confer susceptibility to AITD can be classified into two groups: (1) immune-regulatory genes (e.g., CD40, CTLA-4, and PTPN22); (2) thyroid-specific genes—thyroglobulin and TSH receptor genes. These genes interact with environmental factors, such as infection, likely through epigenetic mechanisms to trigger disease. In this review, we will summarize the latest findings on AITD susceptibility genes in non-Caucasians.
Highlights
Autoimmune thyroid diseases (AITDs) are common autoimmune endocrine diseases [1], and according to one study, AITD are the commonest autoimmune diseases in the USA [2]
The causative variant predisposing to Graves’ disease (GD) is a C/T polymorphism in the Kozak sequence, a nucleotide sequence that is essential for the initiation of translation of the CD40 molecule
Our study demonstrated a weak association between polymorphisms of the FOXP3 gene and AITD in US Caucasians but not in the Japanese
Summary
Autoimmune thyroid diseases (AITDs) are common autoimmune endocrine diseases [1], and according to one study, AITD are the commonest autoimmune diseases in the USA [2]. In GD, the lymphocytic infiltration of the thyroid leads to activation of TSH receptor (TSHR)-reactive B cells that secrete TSHR-stimulating antibodies causing hyperthyroidism [4]. Up until 15 years ago, the only known gene for AITD was HLA-DR3 haplotype (DRB1*03-DQB1*02-DQA1*0501) in Caucasians. In Caucasians, the first locus shown to be associated with AITDs was the HLA-DRB1 locus (reviewed in [5]). HLA-DR3 (DRB1*03) haplotype has been consistently shown to be associated with GD, with an odds ratio (OR) of 2.0 - 3.0 [6,7,8]. Other genes have been shown to influence the expression of GD in Caucasians [13] These include the genes for cytotoxic T lymphocyte-associated protein 4 (CTLA-4) [14,15], CD40 [16], protein tyrosine phosphatase-22. Since most of the studies were performed in relatively small size samples recruited from non-Caucasians, the results have some limited
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