Further, because 6 of 6 individuals who possessed both DR3 and the thyrotropin receptor polymorphism had Graves' disease, while no individual in the normal control group possessed both alleles, study of a larger population to assess the potential synergism between these 2 alleles is warranted.
The prevalence of nonautoimmune hyperthyroidism with TSH receptor mutations is lower than that of latent Graves' disease in TRAb-negative patients with hyperthyroidism.
Fourth, despite many unsuccessful attempts at implicating the TSHR gene as a susceptibility locus for GD, a recent approach of 'tagging' all the common variation within the gene has led to its identification as the first GD specific locus.
Genetic polymorphisms related to GD were identified, levels of thyroid stimulating hormone receptor antibodies (TRAb) were measured, and genetic interactions were assessed by logistic regression analysis.
We have taken the opportunity to examine a population of well-characterized patients with autoimmune thyroid disease (AITD) typed for an additional thyroid susceptibility gene, the immunoregulatory gene for cytotoxic T-lymphocyte antigen 4 (CTLA-4), to examine its relationship with the susceptibility to GD endowed by TSHR gene polymorphisms.
Third, family-based linkage studies led to the mapping of a new type 1 diabetes locus, the PTPN22 gene, which has subsequently been independently replicated as a susceptibility gene for Graves' disease (GD).
Moreover, we identified strong associations of TSHR and major histocompatibility complex class II variants with persistently TRAb-positive Graves' disease.
Although these results cannot eliminate a minor role of the TSHR gene locus in the genetics of Graves' disease, they argue against it being a major genetic determinant in this pathology.
The difference in the association between GD and AA suggests that the CTLA4 and TSHR are not main factors contributing to determining common genetic basis among GD and AA.
Stratifying patients affected with AITDs according to their phenotype (Graves' disease and Hashimoto's thyroiditis) and RA patients according to the presence of rheumatoid factor (RF) and antibodies against cyclic citrullinated peptides (ACPA) did not show any significant association with PTPN22R620W allele (p>0.05).
Therefore, in cases of clustering of non autoimmune hyperthyroidism in families and in cases of sporadic congenital hyperthyroidism with thyroid hyperplasia and no evidence for an autoimmune etiology a search for TSH receptor gene mutations is necessary to appropriately direct the therapy of these patients.
We genotyped the five SNPs (rs12760457, rs2797415, rs1310182, rs2476599, and rs3789604) of the PTPN22 and the two SNPs (rs706778 and rs3118470 in the IL2RA gene) in 456 Japanese patients with AITD (286 with GD, 170 with Hashimoto's thyroiditis) and 221 matched Japanese control subjects.
Familial non-autoimmune hyperthyroidism is a rare autosomal dominant genetic disease resulting from activating mutations in the thyroid-stimulating hormone receptor (TSHR) gene.
T-cell recognition of residue 158-176 in thyrotropin receptor confers risk for development of thyroid autoimmunity in siblings in a family with Graves' disease.
Recently, a single-nucleotide polymorphism (SNP), encoding a functional arginine to tryptophan residue change at PTPN22 codon 620 in Caucasians has been shown to be associated with GD and other autoimmune diseases.
The C allele of rs3789604 (PTPN22) was a significant risk factor for LD-associated hyperthyroidism in GD patients, whereas C allele of GPR174 rs3827440 and G allele of RNASET2 rs9355610 appeared to be a protective factor for this disease.