**5. Medication**

28 Autoimmune Disorders – Current Concepts and Advances from Bedside to Mechanistic Insights

shown the increased familial risk especially for the first-degree relatives and females. In particular, children and siblings of patients with Hashimoto's thyroiditis had a 32-fold and 21-fold increased risk, respectively, for developing immunthyroiditis. In comparison, the risk for developing Graves' disease has been enhanced 7-fold in both children and siblings (10). The high prevalence of AITD in rst degree, foremost female, and relatives of patients with AITD demonstrates the importance of family history for developing AITD. This genetic

Candidate gene analysis, whole-genome linkage screening, genome-wide association studies, and whole-genome sequencing are the major technologies that have advanced this eld, leading to the identication of at least seven genes whose variants have been associated with AITD (11). Using these techniques, 6 AITD susceptibility genes have been identied and conrmed, HLA-DR, CD40, CTLA-4, PTPN22, Thyroglobulin (Tg) and TSH receptor. The AITD susceptibility genes identied so far can be divided into two broad groups: immune modulating genes and thyroid specic genes. The rst group includes the HLA-DR, CD40, CTLA-4, and PTPN22 genes, while the second group includes the Tg and TSH reseptor genes (12). In our previous study, we have studied an association of three polymorphic markers of CTLA-4 gene, namely, C(-318)T, A49G, and (AT)n dinucleotide repeat, which is known the relation with Graves' disease and we reported that A49G

It is clear that additional genes contribute to the genetic susceptibility to AITD, as well as to the different phenotypes of AITD, disease severity, and, possibly, response to therapy but

Several environmental and non-genetic triggers have been implicated in the etiology of HT. These include smoking, stress, iodine excess, medications, bacterial, and viral infections, irradiation, pollutants, and pregnancy. The mechanisms by which certain environmental agents induce thyroid disease could involve interference with thyroid function, direct toxic effects on thyrocytes, or immune stimulation, as well as other effects. It is often difficult to directly link an environmental exposure with thyroid autoimmunity, as disease may be associated with a combination of factors and can manifest over a long period of time. When an environmental exposure triggers HT in individuals with pre-existing thyroid autoantibodies, this may indicate gene-environment interaction, as the presence of thyroid

Iodine is one of the most important precipitants of thyroid dysfunction. Although essential for normal thyroid function, excess iodine supplementation can be associated with the onset of thyroid autoimmunity. Potential mechanisms by which iodine can induce autoimmunity in the thyroid include direct stimulation of immune responses to the thyroid, increased immunogenicity of highly iodinated Tg, and direct toxic effects of iodine on thyrocytes via free oxygen radicals generation (16). A few studies have demonstrated increased incidence of autoimmune thyroiditis in regions where iodine consumption is high according to

Selenium is a trace element that plays an essential role in thyroid hormone synthesis, because two enzymes involved in thyroid hormone production are selenoproteins: the

polymorphism may increase the susceptibility for Hashimoto's thyroiditis (13).

HLA-DR and Tg genes have stronger relation with HT than the others (14).

antibodies is usually a surrogate marker of genetic susceptibility (15).

**3. Iodine** 

**4. Selenium** 

regions with low consumption (16-18).

susceptibility shows necessity of familial regular screening.

Several medications may play a role in the development of HT. Interferon-α, interleukin-2, lithium, amiodarone, and highly active antiretroviral therapy are the agents most commonly associated with thyroid dysfunction (23).
