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Background:  Hashimoto's thyroiditis (HT) is a common autoimmune disease characterized by lymphoid infiltration of the thyroid gland, including both T- and B-cells. Early studies have shown that HT is a complex disorder affected by both environmental and genetic factors. Recently, the single nucleotide polymorphism (SNP) rs2276886 associated with the CXCL9 gene was identified as associated with autoimmune thyroid disease susceptibility in Japanese populations. The aim of the present study was to validate this result for HT in a Chinese Han population.  Methods:  Study subjects, including 688 HT cases and 1456 healthy controls, were recruited, and 10 SNPs located within the CXCL9 gene were genotyped. Genetic association analyses were performed by fitting logistic models. Bioinformatics tools, including RegulomeDB and GTEx were utilized to investigate the functional consequences of the SNPs found to be significantly associated with HT.  Results:  SNP rs2276886 was identified as significantly associated with the risk of HT (odds ratio [OR] = 1.25, p  = 0.0006). No significant expression quantitative trait loci (eQTL) signals could be identified for CXCL9 . Significant eQTL signals were found for other genes, including ART3 , CXCL10 , CXCL11 , NAAA , PPEF2 , and SCARB2 . This SNP physically maps to the CXCL9 gene region; however, further bioinformatic analyses indicated that this SNP might be associated with the gene NAAA .  Conclusions:  The rs2276886 SNP was found to be significantly associated with HT susceptibility. However, our findings suggest that this SNP which maps to the chromosomal region 4q21.1 likely effects the NAAA gene (as opposed to the CXCL9 gene), but still contributes to the susceptibility to HT in Han Chinese populations.

Genetic Polymorphisms on 4q21.1 Contributed to the Risk of Hashimoto's Thyroiditis