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Long Non-coding RNA Genes Polymorphisms H19 (rs2251375) and MALAT1 (rs3200401) Association with Rheumatoid Arthritis and Their Correlation with Disease Activity in a Cohort of Egyptian Patients: A Pilot Study

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Abstract

Rheumatoid arthritis (RA) is a chronic, progressive, inflammatory, autoimmune disease that could be disabling throughout its course. It affects people in their most reproductive years with relatively high morbidity and mortality. Long non-coding RNAs became one of the epigenetic mechanisms to prove a link to RA pathogenesis and development, including H19 and MALAT1 genes. These two genes’ expressions had proved to increase in multiple diseases, attracting attention to their polymorphisms and their possible risk role. Assess the association between H19 SNP (rs2251375) and MALAT1 SNP (rs3200401) and the susceptibility of RA and its disease activity. In this pilot study, 200 hundred subjects (100 RA patients and 100 healthy controls) were investigated for a possible link between the polymorphisms H19 SNP (rs2251375) and MALAT1 SNP (3200401) and RA susceptibility and disease activity. RA-related investigations and clinical assessment were done. Real-time PCR genotyping of both SNPs was done using TaqMan® MGB probes. There was no association between the SNPs and risk of developing RA. However, both SNPs had a significant association with high disease activity. H19 SNP (rs2251375) heterozygous genotype CA had an association with elevated levels of ESR (p = 0.04) and higher DAS28-ESR score (p = 0.03). MALAT1 (rs3200401) C allele had an association with elevated ESR (p = 0.001), DAS28-ESR (p = 0.03), and DAS28-CRP (p = 0.007), while CC genotype had an association with DAS28-CRP (p = 0.015). Linkage disequilibrium and haplotyping of the alleles of both SNPs were analyzed as both genes are present on chromosome 11, but no significant association was found between any of the combinations of the alleles (p > 0.05), denoting that (rs2251375) and (rs3200401) are not in linkage disequilibrium. There is no association between H19 SNP (rs2251375) and MALAT1 SNP (rs3200401) and the susceptibility of RA. However, there is an association between H19 SNP (rs2251375) genotype CA and MALAT1 SNP (rs3200401) genotype CC with RA high disease activity.

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Authors and Affiliations

  1. Clinical Pathology Department, Faculty of Medicine, Suez Canal University, 4.5 km Ring Road, P.O: 41111, Ismailia, Egypt

    Eman Hassan El-Sayed, Amal Fathy, Soha Ezz Al-Deen Younes & Hanan Hassan Omar

  2. Rheumatology, Physical Medicine and Rehabilitation Department, Faculty of Medicine, Suez Canal University, Ismailia, Egypt

    Mohsen Hassan Al-Shahaly

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  1. Eman Hassan El-Sayed
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  2. Amal Fathy
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  3. Soha Ezz Al-Deen Younes
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  4. Mohsen Hassan Al-Shahaly
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Contributions

EHE-S: design the protocol, collect and analyze the data, write the manuscript, and final revision and review the manuscript. AFA-H: collect, analyze and interpret the samples and data, write the manuscript, and final revision and review the manuscript. SEA-DY: acquisition of data, drafting the article and final revision, and reviewing the manuscript. MHA-S: sample collection, drafting the main manuscript, and reviewing the manuscript and final revision. HHO: Design the idea of the study, analyze the data, write the main manuscript and review the manuscript with final approval. All authors have been contributed equally to this work. All authors were involved in the decision to submit the manuscript for publication and had the right to accept or reject comments or suggestions.

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Correspondence to Hanan Hassan Omar.

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Ethical approval for the study was secured by the research ethics committee of the faculty of medicine, Suez Canal University. The study was conducted according to Declaration of Helsinki.

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El-Sayed, E.H., Fathy, A., Al-Deen Younes, S.E. et al. Long Non-coding RNA Genes Polymorphisms H19 (rs2251375) and MALAT1 (rs3200401) Association with Rheumatoid Arthritis and Their Correlation with Disease Activity in a Cohort of Egyptian Patients: A Pilot Study. Biochem Genet 61, 2443–2456 (2023). https://doi.org/10.1007/s10528-023-10383-z

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