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Significant Association of rs77493513 Polymorphism in 3'-UTR of the NRG1 Gene with the Risk of Multiple Sclerosis Disease

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Abstract

Multiple sclerosis (MS) is a chronic inflammatory and autoimmune disease characterized by demyelination of the central nervous system (CNS). Neuregulin 1 (NRG1) is a signaling protein that plays an important role in a variety of biological processes, including potentiate oligodendrocyte differentiation and myelination in the CNS, immune response regulation, and inflammation. Single nucleotide polymorphism (SNP) rs77493513 is located in the untranslated region of the 3' mRNA (3'-UTR) of the NRG1 gene, which is predicted to be the binding site of several microRNAs and may play an important role in post-transcriptional regulation. Study aimed to investigate the association of SNP rs77493513 in the NRG1 gene with the risk of MS disease. In this study, genomic DNA was extracted from whole blood samples of 182 patients with relapsing-remitting multiple sclerosis (RRMS) and 198 controls. Different genotypes of rs77493513 polymorphism were determined using RFLP-PCR technique. Statistical analysis was performed using SPSS 21.0 software and by t, χ2 and logistic regression tests. Our data showed that genotypes AC (OR=3.63, CI= 1.93-6.81, p<0.001) and CC (OR=7.90, CI= 4.13-15.11, p<0.001) significantly increased the risk of MS disease and C allele is risk allele. Also, AC (OR=0.16, CI= 0.04-0.63, p= 0.009) and CC (OR=0.14, CI= 0.03-0.53, p=0.04) genotypes significantly decrease the age of onset of the disease. The results show that allele C of rs77493513 polymorphism in the NRG1 gene can be a risk factor for MS.

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Acknowledgment

Our special thanks to the nurses in the Neurology Division of AL-Zahra Hospital for their cooperation with regard to sampling.

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This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Biology, Faculty of Basic Sciences, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran

    Maedeh Ghorbani & Parisa Mohamadynejad

  2. Department of Genetics, School of Medicine, Kazerun Branch, Islamic Azad University, Kazerun, Iran

    Mehdi Moghanibashi

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  1. Maedeh Ghorbani
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  2. Parisa Mohamadynejad
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  3. Mehdi Moghanibashi
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Contributions

Maedeh Ghorbani participated to sample preparation and carried out the experiments. Parisa Mohamadynejad designed, planned, supervised the project and wrote the manuscript. Mehdi Moghanibashi advised and helped to the interpretation of the results and write the manuscript.

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Correspondence to Parisa Mohamadynejad.

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The authors have no conflict of interest.

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The Institutional Review Board of the Islamic Azad University, Shahrekord Branch approved the study protocol.

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All authors discussed the results and commented on the manuscript. Neither the article nor portions of it have been previously published elsewhere. The manuscript is not under consideration for publication in another journal, and will not be submitted elsewhere until the “Metabolic Brain Disease” editorial process is completed, and all authors consent to the publication of the manuscript in “Metabolic Brain Disease”.

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Ghorbani, M., Mohamadynejad, P. & Moghanibashi, M. Significant Association of rs77493513 Polymorphism in 3'-UTR of the NRG1 Gene with the Risk of Multiple Sclerosis Disease. Metab Brain Dis 37, 1025–1030 (2022). https://doi.org/10.1007/s11011-022-00922-9

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  • DOI: https://doi.org/10.1007/s11011-022-00922-9

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