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Association Between Polymorphisms of IL-23/IL-17 Pathway and Clinical Phenotypes of Autoimmune Thyroid Diseases | ||
| Iranian Journal of Immunology | ||
| مقاله 2، دوره 19، شماره 2، شهریور 2022، صفحه 139-149 اصل مقاله (489.37 K) | ||
| نوع مقاله: Original Article | ||
| شناسه دیجیتال (DOI): 10.22034/iji.2022.93744.2255 | ||
| نویسندگان | ||
| Tiantian Cai1، 2؛ Guofei Wang3؛ Yanping Yang2؛ Kaida Mu2؛ Jing Zhang2؛ Yanfei Jiang2؛ Jin-an Zhang* 2، 4 | ||
| 1Graduate School, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China | ||
| 2Department of Endocrinology & Rheumatology, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai, 201318, People’s Republic of China | ||
| 3Department of Neurosurgery, The First People's Hospital of Xianyang, Xianyang, 712000, Shaanxi Province, People’s Republic of China | ||
| 4Shanghai University of Traditional Chinese Medicine, Shanghai 201203, People’s Republic of China | ||
| چکیده | ||
| 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. | ||
| کلیدواژه‌ها | ||
| Autoimmune Thyroid Diseases (AITD)؛ Gene-gene Interaction؛ Gene-sex Interaction؛ IL-23/IL-17 Pathway؛ Single Nucleotide Polymorphism (SNP) | ||
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