Association Study of the Thyroid Peroxidase Gene in Autoimmune Thyroid Diseases

Abstract Introduction: The etiology of autoimmune thyroid diseases (AITDs), such as Graves’ disease (GD) and Hashimoto’s thyroiditis (HT), is largely unknown. However, genetic susceptibility is believed to play a major role. Recently, a case-control association study performed in Croatia showed a significant association of the single nucleotide polymorphism (SNP) rs11675434 near thyroid peroxidase (TPO) with HT, and also with thyroid autoantibodies against TPO (TPOAb) levels. High TPOAb levels are present in 90% of patients with HT and serve as a clinical marker for the detection of early AITD/HT. Therefore, we conducted a case-control study to determine the genetic association of the rs11675434 near TPO with AITD in a cohort of the Japanese population. Methods: We genotyped the rs11675434 near TPO in 457 Japanese patients with AITD (286 with GD, 171 with HT) and 242 matched Japanese control subjects. The SNP was analyzed using TaqMan probe method, and association study was performed using the χ 2 and Fisher’s exact tests with Yates correction. Results: Both GD and HT showed no significant associations. Moreover, when patients with GD were stratified according to Graves’ ophthalmopathy (GO) (n=96), there were no allelic associations with GO, although there were weak associations between GO and controls (P=0.0494, Odds ratios (ORs)=0.3102). Conclusions: Our finding suggest that the rs11675434 near TPO may not contribute to the risk of AITD in the Japanese population, although the study was in insufficient and underpowered sample size.