Association of miR-499 Polymorphism and Its Regulatory Networks with Hashimoto Thyroiditis Susceptibility: A Population-Based Case-Control Study.
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.
['Tabasi|Farhad|F|0000-0003-4877-0701', 'Hasanpour|Vahed|V|', 'Sarhadi|Shamim|S|', 'Kaykhaei|Mahmoud Ali|MA|0000-0003-2994-4243', 'Pourzand|Pouria|P|', 'Heravi|Mehrdad|M|', 'Langari|Ahmad Alinaghi|AA|0000-0002-3177-9489', 'Bahari|Gholamreza|G|', 'Taheri|Mohsen|M|', 'Hashemi|Mohammad|M|0000-0002-6074-7101', 'Ghavami|Saeid|S|0000-0001-5948-508X']
D000328:Adult D000483:Alleles D001327:Autoimmune Diseases D016022:Case-Control Studies D019295:Computational Biology D005260:Female D005787:Gene Frequency D053263:Gene Regulatory Networks D056726:Genetic Association Studies D020022:Genetic Predisposition to Disease D005838:Genotype D050031:Hashimoto Disease D006801:Humans D007492:Iran D008297:Male D035683:MicroRNAs D008875:Middle Aged D020641:Polymorphism, Single Nucleotide D015995:Prevalence D013959:Thyroid Diseases
mir-499 regulatory network Hashimoto thyroiditis autoimmune thyroid disease (AITD) single nucleotide polymorphism (SNP)