Association of a thyroglobulin gene polymorphism with Hashimoto's thyroiditis in the Japanese population.

The aetiology of the autoimmune thyroid diseases (AITDs), Graves' disease (GD) and Hashimoto's thyroiditis is largely unknown. However, genetic susceptibility is believed to play a major role. Two whole genome scans from Japan and from the USA identified a locus on chromosome 8q24 which showed evidence for linkage with AITD and HT. Recent studies have demonstrated an association between a Tg polymorphisms and AITD, suggesting that Tg is the susceptibility gene on 8q24. We studied 308 Japanese AITD patients (194 GD and 114 HT patients) and 417 Japanese control subjects in association studies. Case-control association studies were performed using D8S284 and D8S272, microsatellite markers located in the 8q24 region, Tgms1 and Tgms2, microsatellite markers in introns 10 and 27, respectively, of Tg, and a SNP in exon 33 of Tg. No differences in allele frequencies were observed between AITD patients and controls for D8S284, D8S272 and Tgms1. Similarly, for Tgms2 and the exon 33 SNP no significant differences in allele frequency distribution were observed for all AITD patients. However, when analysing the HT patients alone we found a significant association between the 330 bp/352 bp genotype of Tgms2 and HT (HT = 16.7%, controls = 7.1%; corrected P-value = 0.01, OR = 2.6). Our results confirm the previous reports of an association between the Tg gene and AITD and suggest that Tg is an AITD susceptibility gene.