Association of miR-499 Polymorphism and Its Regulatory Networks with Hashimoto Thyroiditis Susceptibility: A Population-Based Case-Control Study

Abstract

Hashimoto thyroiditis (HT) is a common autoimmune disorder with a strong genetic background. Several genetic factors have been suggested, yet numerous genetic contributors remain to be fully understood in HT pathogenesis. MicroRNAs (miRs) are gene expression regulators critically involved in biological processes, of which polymorphisms can alter their function, leading to pathologic conditions, including autoimmune diseases. We examined whether miR-499 rs3746444 polymorphism is associated with susceptibility to HT in an Iranian subpopulation. Furthermore, we investigated the potential interacting regulatory network of the miR-499. This case-control study included 150 HT patients and 152 healthy subjects. Genotyping of rs3746444 was performed by the PCR-RFLP method. Also, target genomic sites of the polymorphism were predicted using bioinformatics. Our results showed that miR-499 rs3746444 was positively associated with HT risk in heterozygous (OR = 3.32, 95%CI = 2.00–5.53, p < 0.001, CT vs. TT), homozygous (OR = 2.81, 95%CI = 1.30–6.10, p = 0.014, CC vs. TT), dominant (OR = 3.22, 95%CI = 1.97–5.25, p < 0.001, CT + CC vs. TT), overdominant (OR = 2.57, 95%CI = 1.62–4.09, p < 0.001, CC + TT vs. CT), and allelic (OR = 1.92, 95%CI = 1.37–2.69, p < 0.001, C vs. T) models. Mapping predicted target genes of miR-499 on tissue-specific-, co-expression-, and miR-TF networks indicated that main hub-driver nodes are implicated in regulating immune system functions, including immunorecognition and complement activity. We demonstrated that miR-499 rs3746444 is linked to HT susceptibility in our population. However, predicted regulatory networks revealed that this polymorphism is contributing to the regulation of immune system pathways.

Emerging trends and hot spots in autoimmune thyroiditis research from 2000 to 2022: A bibliometric analysis

“…Emerging evidence suggests that single-nucleotide polymorphisms (SNPs) in immunoregulatory genes may functionally impede the normal development of central and peripheral tolerance and alter the interaction of T cells with antigen-presenting cells (APCs) in the immune synapse. Numerous studies have found that gene polymorphisms, such as CTLA4 ( 93 – 95 ), TNF -308 ( 96 ), TRAF1 ( 97 ), microRNA ( 98 ), NFKB1 ( 99 ), NLRP1 ( 100 ), ICAM-1 ( 101 ), ZFAT ( 102 ) and so on, are significantly associated with AITD. Racial variations in AITD prevalence further accentuate potential genetic polymorphisms and the role of genetic susceptibility in the etiology of AIT ( 103 ).…”

Shared genetic links between hypothyroidism and psychiatric disorders: evidence from a comprehensive genetic analysis

“…About 49% of patients with hypothyroidism have an autoimmune-related etiology ( 7 ). Hashimoto thyroiditis (HT), a chronic autoimmune thyroid disease, is the main cause of hypothyroidism ( 8 ) and has a strong genetic background ( 9 ). These suggested that genetic factors play an important role in the development of hypothyroidism.…”

Association between polymorphisms in miRNAs and ischemic stroke: A meta-analysis

“…MiRNAs broadly regulate physiological and pathological processes in humans, including the process of AS, and may potentially affect the susceptibility to IS through SNPs. Previous evidence suggested that rs2910164, rs2292832, rs11614913, and rs3746444 affected the function of miRNAs, [5][6][7][8][9][10][11] which were shown to be involved in the processes of AS, such as inflammation, [12][13][14][15] endothelial injury, [16][17][18][19] lipid metabolism, [9][10][11] immune response, [19] and angiogenesis. [20][21][22][23][24][25] In addition, miR-146a-3p and miR-149-5p was shown to be involved in the regulation of AS plaque This study was supported by grants from the National Natural Science Foundation of China (81473763), and was supported by grants from the Science Foundation of Heilongjiang University of Chinese Medicine (2017sit01 and2019BS08).…”

“…MiRNAs broadly regulate physiological and pathological processes in humans, including the process of AS, and may potentially affect the susceptibility to IS through SNPs. Previous evidence suggested that rs2910164, rs2292832, rs11614913, and rs3746444 affected the function of miRNAs, [5–11] which were shown to be involved in the processes of AS, such as inflammation, [12–15] endothelial injury, [16–19] lipid metabolism, [9–11] immune response, [19] and angiogenesis. [20–25] In addition, miR-146a-3p and miR-149-5p was shown to be involved in the regulation of AS plaque stability.…”