New Genetic Insights from Autoimmune Thyroid Disease

Abstract

The autoimmune thyroid diseases (AITDs) (Graves' disease and Hashimoto's thyroiditis) are complex genetic diseases which most likely have more than 20 genes contributing to the clinical phenotypes. To date, the genes known to be contributing fall into two categories: immune regulatory genes (including HLA, CTLA4, PTPN22, CD40, CD25, and FCRL3) and thyroid-specific genes (TG and TSHR). However, none of these genes contribute more than a 4-fold increase in risk of developing one of these diseases, and none of the polymorphisms discovered is essential for disease development. Hence, it appears that a variety of different gene interactions can combine to cause the same clinical disease pattern, but the contributing genes may differ from patient to patient and from population to population. Furthermore, this possible mechanism leaves open the powerful influence of the environment and epigenetic modifications of gene expression. For the clinician, this means that genetic profiling of such patients is unlikely to be fruitful in the near future.

Genotype and Phenotype Predictors of Relapse of Graves’ Disease after Antithyroid Drug Withdrawal

“…In addition, we did not analyze all the candidate genes involved in the autoimmune process (e.g. HLA, TSHR, thyroglobulin) [44] and the interaction between the costimulatory genes. These genes and their interaction may have their own impact on outcomes.…”

Thyroid autoimmunity

“…An important e617 Thyroid autoimmunity undertaking, then, is to identify the various genes contributing to this overall heritability. Table III lists the genes which have been so far identified as significantly associated with the AITD and the presence of thyroid antibodies [55]. Interestingly, most of these genes encode proteins which are involved in the economy of the immune system.…”

“…Multiple genes with low contribution statistical value (LOD score) are likely to be involved in the occurrence of AITD and major genes have not been found. It could be that multiple-gene polymorphisms be needed to develop AITD, but the combination modalities between environmental factors and the genetic background are still not known [55].…”

A 50-year Revisit of the Initiation and Associations of Hashimoto’s Disease: Might Findings Conform to a Concept of Multifactorial Physiopathologic Transitions?

“…However, a 2009 report 37 based on the Swedish national multigeneration register database indicated standardized incidence ratios (SIR) of RA in a family member, when the proband's disease was Hashimoto thyroiditis/hypothyroidism. 12,38,39 .…”