MIR149 rs2292832 and MIR499 rs3746444 Genetic Variants Associated with the Risk of Rheumatoid Arthritis

Yasir Ali; Yangchao Chen; Zia Ul Islam; Aisha Aman; Mashal M Almutairi; Abdulaziz Alouffi; Aymen Mohammed; Aftab Ali Shah; Zia Ur Rehman; Ibrar Hussain; Abid Ali; Fazal Jalil

doi:10.3390/genes14020431

MIR149 rs2292832 and MIR499 rs3746444 Genetic Variants Associated with the Risk of Rheumatoid Arthritis

Genes (Basel). 2023 Feb 8;14(2):431. doi: 10.3390/genes14020431.

Authors

Yasir Ali^{1

2}, Yangchao Chen², Zia Ul Islam¹, Aisha Aman¹, Mashal M Almutairi³, Abdulaziz Alouffi⁴, Aymen Mohammed⁵, Aftab Ali Shah⁶, Zia Ur Rehman⁷, Ibrar Hussain⁸, Abid Ali⁹, Fazal Jalil¹

Affiliations

¹ Department of Biotechnology, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan.
² School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong 999077, China.
³ Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
⁴ King Abdulaziz City for Science and Technology, Riyadh 12354, Saudi Arabia.
⁵ Division of Molecular Therapeutics and Formulation, School of Pharmacy, University of Nottingham, Nottingham NG7 2RD, UK.
⁶ Department of Biotechnology, Faculty of Biological Sciences, University of Malakand, Chakdara 18800, Pakistan.
⁷ Peshawar Medical College, Peshawar 25160, Pakistan.
⁸ Department of Medicine, Lady Reading Hospital (LRH), Peshawar 25000, Pakistan.
⁹ Department of Zoology, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan.

Abstract

Introduction: MicroRNAs (miRNAs) are small non-coding RNAs that play a key role in post-transcriptional modulation of individual genes' expression. Several miRNA variants from different populations are known to be associated with an increased risk of rheumatoid arthritis (RA).

Aim: This study was undertaken with the aim to investigate the association of single nucleotide variants; namely, rs2292832, rs3746444, rs11614913, rs1044165, and rs767649 of MIR149, MIR499, MIR196, MIR223, and MIR155, respectively, with RA in the Pakistani population.

Methods: A case-control study was performed by recruiting and genotyping a total of 600 individuals (300 cases and 300 controls) for these five variants using a TaqMan single-nucleotide polymorphism (SNP) genotyping assay. The resultant genotypic data was statistically analyzed through a chi-squared test for its association with RA under different inheritance models.

Results: We found a significant association of rs2292832 with RA at genotypic (co-dominant (p < 0.0001), dominant (CC vs. TT + CT: OR 2.063 (1.437-2.962); p = 0.0001), recessive (TT vs. CT + CC: OR 0.376 (0.259-0.548); p < 0.0001)), and allelic (allele C) levels ((OR 0.506 (0.402-0637); p < 0.0001)). Similarly, the rs3746444 showed a significant association with RA under co-dominant (p = 0.0001), dominant (GG vs. AA + AG: OR 5.246 (3.414-8.061); p < 0.0001), recessive (AA vs. GG + AG: OR 0.653 (0.466-0.916); p = 0.014), and additive models (G vs. A; OR 0.779 (0.620-0.978); p = 0.03). However, we did not observe any significant association of rs11614913, rs1044165, or rs767649 with RA in our subjects.

Conclusion: To our knowledge, this was the first study that investigated and found an association between functional polymorphisms in miRNAs and RA in the Pakistani population.

Keywords: genotyping; miRNAs; rheumatoid arthritis; variants.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Arthritis, Rheumatoid* / genetics
Case-Control Studies
Genetic Predisposition to Disease
Humans
MicroRNAs* / genetics
Polymorphism, Single Nucleotide

Substances

MicroRNAs
MIRN149 microRNA, human
MIRN499 microRNA, human

Grants and funding

Y.A. was supported by the International Research Support Initiative Program (IRSIP) of the Higher Education Commission of Pakistan. The authors acknowledge the support of the School of Biomedical Sciences of The Chinese University of Hong Kong. The researchers supporting project number (RSP2023R494), King Saud University, Riyadh, Saudi Arabia. The study also was sponsored by the Higher Education Commission, Pakistan (project number NRPU# 5203).