Table 2.
Some Possible Mechanisms for the Thyroid Stimulating Hormone Receptor Gene Association with Graves' Disease
| 1. Nonsynonymous changesa |
| • Residue change affecting posttranslational modifications and altered receptor half-life and enhanced immune response. |
| • Changes increasing peptide affinity for HLA binding, thus influencing antigen presentation. |
| 2. Spliced variants |
| • Variants with intrinsic activity, for example, kinase. |
| • Variants with structural impact on the immune response. |
| 3. Small RNAs |
| • Regulating TSH receptor expression/life cycle. |
| • Regulating immune reactivity to the TSHR. |
| 4. Linkage disequilibrium with another gene |
| • Influence on genes of immune regulation leading to reduced immune tolerance. |
a
No consistent evidence has been found to date for any changes in TSHR residues associated with Graves' disease.