Autoimmune thyroid disease, genetic predisposition and environment – case-control and family studies

Background: Up to 25% of the European population are target of thyroid diseases with an increasing number of autoimmune thyroid diseases (AITD) such as Hashimoto's or Graves' disease. A strong genetic background has been presumed due to the aggregation in families and the occurrence of thyroid autoantibodies in about 50% of „healthy“ relatives. We evaluated genetic predisposition defined by allelic variants of genes involved in the regulation of inflammation and environmental factors in AITD.

Methods: 223 cases with age and gender matched controls and 26 families were investigated for medical history, anthropometric data, thyroid ultrasound pattern, thyroid function and biochemical markers including selenium serum and iodine urinary values. Loci investigated were located in the CTLA4 (cytotoxic T lymphocyte antigen 4), MHC2TA (major histocompatibility class II transactivator) and VDR (vitamin D receptor) genes.

Results: Patients and controls (both mean age 43±16 years, 92% females) showed significant differences in thyroid function and generally low selenium levels. In patients, significant negative correlations were found for thyroid volume and age (p=0.035). Loci associated with autoimmune thyroid disease were CTLA4–60, CTLA4-MH30, and MHC2TA with selenium for thyroid volume in families.

Conclusions: AITD is associated with allelic variations of the CTLA4 and other candidate genes; environmental factors such as selenium might enhance AITD manifestation. Therefore, future thyroid diagnosis might include genetic risk factors as well. Further genetic loci in AITD are under investigation.