Hashimoto's thyroiditis

General disease information: According to Wikipedia (2017), in areas of the world with sufficient dietary iodine, hypothyroidism is most commonly caused by the autoimmune disease Hashimoto's thyroiditis (chronic autoimmune thyroiditis), a disease in which the thyroid gland does not produce enough thyroid hormone. It can cause a number of symptoms, such as poor ability to tolerate cold, a feeling of tiredness, constipation, depression, and weight gain. (Wikipedia page edited July 22, 2017)

[PMID 22654557] A 2011 article called "Hashimoto's Thyroiditis: From Genes to the Disease" explained that "Hashimoto’s thyroiditis (HT) is the most prevalent autoimmune thyroid disorder", and is "recorded in 4% to 9.5% of the adult population." In the progress of this disease, "Intrathyroidal lymphocytic infiltration is followed by a gradual destruction of the thyroid gland which may lead to subclinical or overt hypothyroidism." ... Genes for human leukocyte antigen (HLA), cytotoxic T lymphocyte antigen-4 (CTLA4), protein tyrosine phosphatase nonreceptor-type 22 (PTPN22), thyroglobulin, vitamin D receptor, and cytokines are considered to be of utmost importance."

[PMID 23617710] A 2013 article titled "How far are we from understanding the genetic basis of Hashimoto's thyroiditis?" explained that "Because of the complex nature of AITD (Autoimmune thyroid disease), caused by their polygenic nature and a complex mode of inheritance, there are still more questions to be answered than answers that can be given, especially about the nature of Hashimoto's thyroiditis. There are plenty of papers concerning the pathogenesis of AITD. However, not seldom do they end up in conclusions about GD (Graves' disease), because the results for this disease are far clearer and more unambiguous than those obtained for HT. Similarly, meta-analyses and especially reviews most often concentrate on AITD in general or on GD alone." (Abstract).

• In the extended abstract of [PMID 23617710] published with open access via BioMed Central, the article listed the following mutations that predispose to autoimmune diseases (not just Hashimoto's):
  • The PTPN22 c.1858C>T polymorphism (also notated as C1858T: this is the minor/risk allele of rs2476601, which is associated with multiple autoimmune disorders
  • The CTLA4 c.49A>G polymorphism (A49G: This is rs231775, and again the minor allele is the risk allele)
  • The CT60 c.6230A>G polymorphism (A6230G: This is the rs3087243 minor allele. It is also part of the CTLA4 gene.)
  • The TG (Thyroglobulin) gene, several SNP risk alleles, if found together, among the "exons 10-12 SNP cluster" and "an exon 33 SNP" AND an amino acid signature in the HLA-DRB1 gene's exon 2. "The article explained that "In contrast to many other autoimmune diseases, it was impossible to unanimously associate HT with one HLA-DR type." (Extended abstract).
  • The TG Thyroglobulin gene -1623 polymorphism (A1623G, at rs180195). "Carriers of the susceptibility allele at position -1623 of the TG promoter region are prone to produce high amounts of TG when encountering IFNα" (Extended abstract).

For more information, see the pages on Autoimmune thyroiditis and Hypothyroidism