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Association analysis of miRNA-146a and miRNA-499 polymorphisms with rheumatoid arthritis: a case–control and trio-family study

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Abstract

Single nucleotide polymorphism is known to alter the expression and processing of miRNAs leading to a variety of diseases including rheumatoid arthritis (RA). However, disagreement is present up to date regarding the association of miRNA-146a and miRNA-499 polymorphisms with RA. The goal of this study was to assess the association of polymorphisms at miRNA-146a and miRNA-499 with the pathogenesis of RA in patients originating from Pakistan. Initially, eleven hundred subjects (1100) comprises of 550 RA patients and 550 healthy controls were investigated in the case–control analysis. Spectrophotometric measurement of lipids and C-reactive protein was used, whereas interleukin-1 receptor associated kinase-1 and TNF-receptor associated factor-6 values were quantified by an enzyme-linked immunosorbent assay. Secondly, heritability of susceptible alleles was tested from 70 trio-families. The miRNA-146a rs2910164 and miRNA-499 rs3746444 polymorphisms were genotyped using the polymerase chain reaction followed by restriction digestion. A Significant association of miRNA-146a and miRNA-499 genotypes was observed with RA patients (P < 0.05, respectively). The miRNA-146a rs2910164 G (OR = 1.4, P < 0.05) and miRNA-499 rs3746444 C (OR = 1.6, P < 0.0001) allele was significantly associated with RA in comparison with controls, respectively. Besides, the transmission analysis revealed a significant (P < 0.05) inheritance of rs2910164 G and rs3746444 C allele from parents to affected offspring. The current research concludes that miRNA-146a (rs2910164; C > G) and miRNA-499 (rs3746444; T > C) polymorphisms are linked to RA in the population studied. Furthermore, it was demonstrated for the first time in our high-risk cohort that the rs2910164 G and rs3746444 C allele was strongly related to familial RA.

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Data availability

The data used to support the current results are included in this article. For more information please contact at sabirhussain@comsats.du.pk.

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Acknowledgments

The authors acknowledge all the volunteers and participants of the study and COMSATS University Islamabad for providing the facilities. The current research was partially supported by COMSATS University Islamabad, Pakistan under general Laboratory funds for the Department of Biosciences.

Funding

The study was conducted in COMSATS University Islamabad.

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Authors and Affiliations

  1. Department of Biosciences, COMSATS University Islamabad, Park Road, Tarlai Kalan, Islamabad, 45550, Pakistan

    Zia Ul Islam, Umul Baneen, Syed Muhammad Nurulain, Zahid Muneer & Sabir Hussain

  2. Department of Rheumatology, Federal Government Polyclinic Hospital, 44 Luqman Hakeem Road G/6, Islamabad, 46000, Pakistan

    Taqdees Khaliq

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  1. Zia Ul Islam
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  2. Umul Baneen
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  3. Taqdees Khaliq
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  4. Syed Muhammad Nurulain
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  6. Sabir Hussain
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Contributions

All authors contributed to the design and concept of proposed study. Materials were provided by S H, S M N, and Z M. The samples diagnosis and collection were done by T K, and the processing was done by Z u I, and U B. Experiments were conducted by Z U I, U B. Statistical analysis and paper writing was done by S H, S M N, and Z M. All authors read and approved the manuscript for submission.

Corresponding author

Correspondence to Sabir Hussain.

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The authors declare that they have no conflict of interest.

Ethical approval.

This study was conducted via a collaboration between COMSATS University Islamabad and Federal Government Polyclinic hospital Islamabad, Pakistan. Approvals were obtained from the ethical review committees and institutional review boards of both the institutes according to the Declaration of Helsinki revised in 2013.

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Signed written informed consent was obtained from all the participants of the study.

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Ul Islam, Z., Baneen, U., Khaliq, T. et al. Association analysis of miRNA-146a and miRNA-499 polymorphisms with rheumatoid arthritis: a case–control and trio-family study. Clin Exp Med 23, 1667–1675 (2023). https://doi.org/10.1007/s10238-022-00916-y

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  • DOI: https://doi.org/10.1007/s10238-022-00916-y

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