At this stage, we cannot exclude the Tg region as harboring a susceptibility locus for AITD, and only large scale sequencing and fine mapping of the region, including neighboring genes, will allow us to identify any potential causal variants within this region.
(2) Haplotype analysis of these four SNPs revealed that the G-C-A-C haplotype was significantly associated with HT (P < 0.01, OR = 3.06, OR 95% CI [1.326-7.089]) and with serum anti-Tg antibody (Tg-Ab) positive AITD patients (P = 0.028, OR = 3.34).
Three loci showed evidence for linkage with TAb production: 1) 2q locus, which gave a maximum multipoint heterogeneity LOD score (HLOD) of 2.8 and contained the CTLA-4 gene, previously reported to be linked and associated with clinical AITD; (2) 6p locus (HLOD 2.5), which was the same AITD-1 locus found to be linked with clinical AITD; and (3) 8q locus (HLOD 2.2), which contained the thyroglobulin gene, also previously reported to be linked and associated with AITD.
Analysis of positional candidate genes strongly supported CTLA-4 as the gene on 2q associated with APS3v and FOXP3 as the gene on Xp associated with T1D or AITD and APS3v.
The number of identified susceptibility genes for AITD is increasing (among others now including TSHR, TG, HLA, CTLA4, PTPN22, CD40, FCRL3, IL2RA, and FOXP3), but these genes together probably do not explain more than about 10% of the heritability of AITD.
Autoimmune thyroid disease (AITD), including Hashimoto's thyroiditis (HT) and Graves' disease (GD), is the most common autoimmune disorder in the United States, affecting over 20 million people.
The TSHR-AT marker showed association in this Japanese AITD population with a significant increase in allele 5 (294 bp; p < 0.05) and a significant decrease in allele 7 (298 bp; p < 0.05).
In conclusion, our work showed the association between the thyroglobulin gene and autoimmune thyroiditis in Argentinian population and supports the described evidence of thyroglobulin as a thyroid-specific gene linked to AITD.
Genome-wide association studies have revealed several susceptibility genes among patients with autoimmune thyroid disease (AITD), including CTLA4, PTPN22, FCRL3, and ZFAT.
Susceptibility genes for autoimmune thyroid disease (AITD) have been investigated, although only the human leukocyte antigen and cytotoxic T lymphocyte-associated antigen-4 gene regions have been consistently associated with disease.
Given the high frequency of AITD in patients with type 1 diabetes, these data suggest the possibility that the association of CTLA4 with type 1 diabetes in previous studies may have been secondary to AITD, suggesting the importance of subclassification of type 1 diabetes relative to AITD in genetic studies.
Autoimmune thyroid disease (AITD), including Graves' disease (GD), Hashimoto thyroiditis (HT), and primary idiopathic myxedema, is caused by multiple genetic and environmental factors.
Our data show a significant effect of the CTLA4 CT60G allele at the homozygous state on the risk of developing AITD in children with CD and suggest that the reported association of the CTLA4 CT60 A/G polymorphism with CD is limited to the subgroup of patients who are or will be complicated with AITD.
Autoimmune thyroid disease (AITD), which is characterized by an increased presence of thyroid autoantibodies (TAbs), such as antibodies against thyroid peroxidase (TPOAbs) and antibodies against thyroglobulin (TgAbs), has been reported to be associated with rheumatoid arthritis (RA) because AITD and RA both involve autoimmunity.
Three loci showed evidence for linkage with TAb production: 1) 2q locus, which gave a maximum multipoint heterogeneity LOD score (HLOD) of 2.8 and contained the CTLA-4 gene, previously reported to be linked and associated with clinical AITD; (2) 6p locus (HLOD 2.5), which was the same AITD-1 locus found to be linked with clinical AITD; and (3) 8q locus (HLOD 2.2), which contained the thyroglobulin gene, also previously reported to be linked and associated with AITD.
Several allele and genotype frequencies differed between the AITD group and the healthy control group (Tg E10SNP: Allele T, P<0.01; allele G, P<0.01; and Tg genotype GG, P<0.01; genotype TG, P<0.01.
Autoimmune thyroid disease (AITD) comprises diseases including Hashimoto's thyroiditis and Graves' disease, both characterized by reactivity to autoantigens causing, respectively, inflammatory destruction and autoimmune stimulation of the thyroid-stimulating hormone receptor.
The production of animal TSHR monoclonal antibodies (MAbs) with the characteristics of patient autoantibodies and the isolation of human autoantibodies from patients with AITD has allowed us to analyze the interactions of these antibodies with the TSHR at the molecular level.