@article { author = {Cai, Tiantian and Wang, Guofei and Yang, Yanping and Mu, Kaida and Zhang, Jing and Jiang, Yanfei and Zhang, Jin-an}, title = {Association Between Polymorphisms of IL-23/IL-17 Pathway and Clinical Phenotypes of Autoimmune Thyroid Diseases}, journal = {Iranian Journal of Immunology}, volume = {19}, number = {2}, pages = {139-149}, year = {2022}, publisher = {Shiraz Institute for Cancer Research}, issn = {1735-1383}, eissn = {1735-367X}, doi = {10.22034/iji.2022.93744.2255}, abstract = {Background: Several autoimmune and inflammatory disorders, including autoimmune thyroid diseases (AITD), have been linked to Th17 cells and the IL-23/IL-17 axis. Current data suggest that genetic variation contributes greatly to disease susceptibility to AITD. Objectives: To study the role of single nucleotide polymorphisms (SNPs) of IL-23/IL-17 pathway in AITD predisposition and test the gene-gene/gene-sex interactions in these loci. Methods: A total of 1051 patients with AITD, including 657 patients with Graves' disease (GD) and 394 patients with Hashimoto's thyroiditis (HT), and 874 healthy controls were enrolled in this case-control association study. Six SNPs were selected and genotyped by multiplex PCR combined with high-throughput sequencing. Interactions were tested by the general multifactor dimensionality reduction (GMDR) method. Results: Allele C and combinational genotype AC+CC of rs3212227 within IL-23 were significantly associated with GD with goiter (p=0.003 and 0.014, respectively). Allele G and combinational genotype AG+GG of rs4819554 within IL-17RA were significantly related to HT with family history and the severity of HT (p=0.011 and 0.027; p=0.041 and 0.035). Also, allele T and genotype CT+TT of rs9463772 within IL-17F were significantly correlated with the severity of HT (p=0.001 and 0.027, respectively). Moreover, high dimensional gene-sex interaction (IL-23R-IL-23-IL-17RA-IL-17F-sex) was identified in AITD, GD, and HT patients with GMDR analysis. Conclusions: Our study identified the novel loci and gene-sex interaction in AITD. This evidence, from another perspective, suggests that sex, IL-23/IL-17 pathway, and Th17 cells play an important role in the pathogenesis of AITD.}, keywords = {Autoimmune Thyroid Diseases (AITD),Gene-gene Interaction,Gene-sex Interaction,IL-23/IL-17 Pathway,Single Nucleotide Polymorphism (SNP)}, url = {https://iji.sums.ac.ir/article_48511.html}, eprint = {https://iji.sums.ac.ir/article_48511_af716187af161b73bfc029f9508142b1.pdf} }