Association between IL-6, miRNA-146a, MALAT1 genetic polymorphisms and risk of rheumatoid arthritis
Creators: name: Ali, Yasser BM
name: Hasan, Noura MA
name: El-maadawy, Eman A
name: Bassyouni, Iman H
name: EL-Shahat, Mohamed
name: Talaat, Roba M
Publisher: name: Taylor & Francis
Year: 2024
Subjects: subject: Genetics
subject: FOS: Biological sciences
subject: Molecular Biology
subject: Neuroscience
subject: Ecology
subject: Immunology
subject: FOS: Clinical medicine
subject: Developmental Biology
subject: Cancer
subject: Mental Health

description: <b>Aim:</b> This study aimed to investigate the associations between single nucleotide polymorphisms (SNPs) of <i>IL-6</i> (-174G/C), <i>microRNA146a</i> (rs2910164C/G) and <i>MALAT1</i> (rs619586A/G) and susceptibility to rheumatoid arthritis (RA) in Egyptians. <b>Methods:</b> SNPs were genotyped in 101 RA patients and 104 controls. Expression levels were evaluated either by Enzyme-linked immunosorbent assay (ELISA) for IL-6 or quantitative real-time PCR (qRT-PCR) for miR-146a and MALAT1. <b>Results:</b><i>IL-6–174</i> GC (OR = 3.422) genotype, IL-6–174 C allele (OR = 2.565), miR-146a (rs2910164) CG (OR = 2.190) and MALAT1 (rs619586) AA (OR = 4.125) genotypes and A allele (OR = 6.122) could be considered as risk factors for RA. An increase in the expression of IL-6, miR-146a and MALAT1 was detected in RA patients, which was independent of any SNP. <b>Conclusion:</b> SNPs of IL-6, miR-146a and MALAT1were linked to RA predisposition in Egyptians. Rheumatoid arthritis (RA) is a chronic joint disorder with overexpression of inflammatory mediators. There is increasing evidence that epigenetic changes could play a prominent role in RA pathogenesis. This study was designated to explore the associations between genetic mutation of inflammatory cytokines (Interleukin (<i>IL-6</i>) and epigenetic modulators (<i>miR-146a</i> and <i>MALAT1</i>) and susceptibility to RA. Increased production of IL-6, miR-146a and MALAT1 is a remarkable event in RA patients. We provide evidence that certain genotypes could be used as risk factors for the disease. Our data suggest that detecting certain mutations is quite important in disease prediction. Special concern has to be directed to those persons harboring definite genotypes to achieve better clinical manipulation of patients at risk. This study demonstrated an elevation in IL-6, miR-146a and MALAT1 in RA patients. Moreover, we found that susceptibility to RA is associated with <i>IL-6</i> (rs1800795) GC, <i>miR-146a</i> (rs2910164) CG and <i>MALAT1</i> (rs619586) AA genotypes. <i>IL-6</i> (-174G/C), <i>miR-146a</i> (rs2910164C/G) and <i>MALAT1</i> (rs619586A/G) SNPs were thought to be associated with RA risk. This study aimed to investigate this association with RA in Egyptians. in 101 RA patients and 104 controls. <i>IL-6</i> (-174G/C) was genotyped utilizing MS-PCR, <i>miR-146a</i> (rs2910164 C/G) and <i>MALAT1</i> (rs619586 A/G) was genotyped using RFLP-PCR. Expression levels were evaluated either by ELISA for IL-6 or qRT-PCR for miR-146a and MALAT1. The statistical analysis showed that IL-6–174GC genotype, C allele and miR-146a (rs2910164) CG genotype were significantly increased in patients versus controls (<i>p &lt;</i> 0.01, <i>p &lt;</i> 0.05, <i>p &lt;</i> 0.01; respectively). Patients showed a significant reduction in IL-6–174GG (<i>p &lt;</i> 0.05), miR-146a (rs2910164) CC genotypes (<i>p &lt;</i> 0.05) and MALAT1(rs619586) G allele (<i>p &lt;</i> 0.05) compared with controls. The genotypes of IL-6–174GC, miR-146a rs2910164 CG and MALAT1 rs619586AA could all be considered risk factors for RA. CGA haplotype was significantly increased (<i>p &lt;</i> 0.01) in patients than in healthy ones. A significant elevation of IL-6, miR-146a and MALAT1 expression levels was detected in RA patients (<i>p &lt;</i> 0.001, <i>p &lt;</i> 0.05 and <i>p &lt;</i> 0.001, respectively). miR-146a was positively correlated with MALAT1 (r = 0.326, <i>p &lt;</i> 0.05) in RA patients.