Autoimmune thyroid diseases (AITDs), including Graves’ disease (GD) and Hashimoto’s thyroiditis (HT), are caused by immune response to self-thyroid antigens and affect approximately 2–5% of the general population. Genetic susceptibility in combination with external factors, such as smoking, viral/bacterial infection, and chemicals, is believed to initiate the autoimmune response against thyroid antigens. Abundant epidemiological data, including family and twin studies, point to a strong genetic influence on the development of AITDs. Various techniques have been employed to identify genes contributing to the etiology of AITDs, including candidate gene analysis and whole genome screening. These studies have enabled the identification of several loci (genetic regions) that are linked to AITDs, and, in some of these loci, putative AITD susceptibility genes have been identified. Some of these genes/loci are unique to GD and HT and some are common to both diseases, indicating that there is a shared genetic susceptibility to GD and HT. Known AITD-susceptibility genes are classified into three groups: HLA genes, non-HLA immune-regulatory genes (e.g., CTLA-4, PTPN22, and CD40), and thyroid-specific genes (e.g., TSHR and Tg). In this paper, we will summarize the latest findings on AITD susceptibility genes in Japanese. 1. Introduction 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]. Even though the hallmark of AITD is infiltration of the thyroid with thyroid reactive lymphocytes, the end result is two clinically opposing syndromes: Hashimoto’s thyroiditis (HT) manifesting by hypothyroidism and Graves’ disease (GD) manifesting by hyperthyroidism. In HT, the lymphocytic infiltration of the thyroid gland leads to apoptosis of thyroid cells and hypothyroidism [3]. In contrast, 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]. GD and HT are complex diseases, and their etiology involves both genetic and environmental influences [1]. Up until 15 years ago, the only known gene for AITD was HLA-DR3 haplotype (DRB1*03-DQB1*02-DQA1*0501) in Caucasians. However, with the advent of new genomic tools and the completion of the human genome and the HapMap projects, new non-HLA genes have been identified and their functional effects on disease aetiology started to be dissected as well. This paper will summarize the recent advances
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