Endocrine Abstracts

Background: The autoimmune thyroid diseases, primary autoimmune hypothyroidism (AH) and Graves’ hyperthyroidism (GD), represent the most prevalent endocrine disorders. Although clinically distinct, they share several genetic susceptibility loci, many of which remain unidentified.

TIGIT (T cell immunoreceptor with immunoglobulin and ITIM domains), expressed on the surface of T-cells, interacts with CD-155 on dendritic cells to form an alternative costimulatory pathway. It therefore drives a more tolerogenic phenotype making it a plausible candidate gene for autoimmune diseases. A TIGIT variant in the canine genome has been associated with lymphocytic thyroiditis in a genome-wide meta-analysis in the Rhodesian Ridgeback and Dobermann pedigree dogs (unpublished data), however no links to human thyroid diseases have been established.

Hypothesis: We hypothesise that variants in TIGIT may be associated with susceptibility to GD in humans.

Subjects and Methods: We performed a case-control association study of two TIGIT single nucleotide polymorphisms (SNPs; rs10934259 and rs2693052). These were genotyped using Taqman chemistry (Life Technologies) in 426 GD patients. Results were compared to data from 5097 healthy individuals available from the Wellcome Trust (WTCCC2) using PLINK.

Results: For rs10934259, the AA genotype was present in 48 cases (12%) compared to 567 controls (11%). 186 cases (46%) and 2353 controls (46%) were heterozygous. The frequency of the minor A allele was 0.35 and 0.34 in cases and controls respectively (P >0.05). For rs2693052, the TT genotype was present in 75 cases (18%) compared to 833 controls (16%). 178 cases (42%) were heterozygous compared to 2409 controls (47%). The frequency of the minor T allele was 0.39 and 0.40 in cases and controls respectively (P >0.05).

Conclusions: This study suggests that TIGIT is not playing a significant role in susceptibility to GD in humans. Further studies are now needed to determine whether TIGIT variants contribute to susceptibility to AH.