Association of AITD with Microsatellite Markers for TSHR and CTLA-4 in Japanese Patients

Abstract

We examined the genetic contribution of the thyrotropin receptor (TSHR) gene to autoimmune thyroid disease (AITD) in Japanese patients. We identified a dinucleotide repeat polymorphism near the TSHR gene which was mapped to an 8.6 cM interval between D14S74 and D14S55 on the long arm of human chromosome 14. TSHR-CA has been mapped to approximately 600kb of the TSHR gene using the radiation hybrid mapping. Initial studies with this marker, TSHR-CA, revealed a significant association between AITD and one specific allele (allele 1) of the micro satellite sequence in 81 unrelated Japanese AIID patients and 113 Japanese controls (Sale et al., Proc. Assoc. Am. Physicians, 109:453, 1997). In a second study, TSHR-CA and another TSHR microsatellite marker, TSHR-AT, which is located in intron 2 of TSHR gene (de Roux et al., Mol Cell Endocrinol, 117:253, 1996), were genotyped in a set of 349 unrelated Japanese AITD patients and 218 Japanese controls. The TSHR-AT marker showed an 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). The association of allele 5 of TSHR-AT was also significant in hypothyroid patients (TBII+, P < 0.01; TBII-, P < 0.05), as was .the association of allele 7 of TSHR-AT (P < 0.05). Associations with TSHR-CA were observed in patients with Hashimoto’s thyroiditis (HT) with respect to alleles 3 (179 bp; P < 0.05) and 5 (175 bp; P < 0.05) and with hypothyroid TBII- patients for allele 4 (177 bp; P < 0.05). (Akamizu et al. Thyroid, 10: 851,2000).