Endocrine Abstracts

The autoimmune thyroid diseases (AITDs), Graves' disease (GD) and Hashimoto's thyroiditis (HT), are thought to be caused by complex interactions between genetic and environmental factors, which result in an organ-specific autoimmune response being directed against the thyroid gland. GD and HT, although clinically distinct, share many immunological and histological features. Several potential susceptibility genes for AITD have been investigated, although to date only the HLA and CTLA-4 gene regions have been consistently associated with disease. Recent data however, has shown linkage and association of chromosome 8q24 with AITD. Thyroglobulin (Tg), a glycoprotein precursor to the thyroid hormones, has been mapped to this region, making chromosome 8q24 a thyroid-specific candidate gene region for AITD. We, therefore, performed a case-control association study on 855 subjects with AITD and 790 controls using previously associated microsatellite markers in the 8q24 region, D8S284 and Tgms2 (in intron 27 of Tg). Both markers were genotyped using a fluorescence-based technology. No differences in allele frequencies were observed between cases and controls for D8S284 (size range 244-276bp). Similarly, for Tgms2 (size range 326-364bp), no significant differences in allele frequencies were observed between cases and controls, when analysing alleles separately (power >99.9%). When considering rare Tgms2 alleles (frequency <10%) as a group, evidence was found for association with AITD (chi-square = 10.54, p = 0.001). Specifically, the 336bp allele previously associated with AITD, was more frequent in AITD cases compared with controls 2.2% v 0.25% (chi-square = 24.9, p = <0.001, uncorrected). The association of a rare allele of the Tgms2 marker in our UK data set replicates the original finding in a USA cohort. However, because of the low frequency of this allele, further studies are required to exclude the alternative explanations of population mismatch and random chance event.