Which genes are implicated in the pathogenesis of in Graves disease?

Updated: Apr 17, 2020
  • Author: Sai-Ching Jim Yeung, MD, PhD, FACP; Chief Editor: Romesh Khardori, MD, PhD, FACP  more...
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Several autoimmune thyroid disease susceptibility genes have been identified: CD40, CTLA-4, thyroglobulin, TSH receptor, and PTPN22. [4, 5] Some of these susceptibility genes are specific to either Graves disease or Hashimoto thyroiditis, while others confer susceptibility to both conditions. The genetic predisposition to thyroid autoimmunity may interact with environmental factors or events to precipitate the onset of Graves disease.

Two new susceptibility loci were found: the RNASET2-FGFR1OP-CCR6 region at 6q27 and an intergenic region at 4p14. [6] Moreover, strong associations of thyroid-stimulating hormone receptor and major histocompatibility complex class II variants with persistently thyroid stimulating hormone receptor autoantibodies (TRAb)-positive Graves disease were found. [7]

Graves disease patients a have higher rate of peripheral blood mononuclear cell conversion into CD34+ fibrocytes compared with healthy controls. These cells may contribute to the pathophysiology of ophthalmopathy by accumulating in orbital tissues and producing inflammatory cytokines, including TNF-alpha and IL-6. [8] In a genome-wide association study of more than 1500 Graves disease patients and 1500 controls, 6 susceptibility loci were found to be related to Graves disease (major histocompatibility complex, TSH receptor, CTLA4, FCRL3, RNASET2-FGFR1OP-CCR6 region at 6q27, and an intergenic region at 4p14. [9]

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