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Could NCOA5 a novel candidate gene for multiple sclerosis susceptibility?

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Abstract

Background

Multiple sclerosis (MS) is an inflammatory immune-mediated demyelinating disease that causes a challenging and disabling condition. Environmental and genetic factors play a role in appearing the state of the disease. Recent studies have shown that nuclear cofactor genes may play a role in the pathogenesis of MS. NCOA5 is a nuclear receptor coactivator independent of AF2 that modulates ERa-mediated transcription. This gene is involved in the pathogenesis of diseases such as psoriasis, Behcet’s disease, and cancer.

Methods and results

We investigated the relationship between the rs2903908 polymorphism of the NCOA5 gene and MS among 157 unrelated MS patients and 160 healthy controls by RT-PCR. The frequencies of the CC, CT, and TT genotypes were 19.87%, 37.82%, and 42.31%, respectively, for the MS group and 5.63%, 43.75%, and 50.62%, respectively, for the control group. The CC genotype and the C allele were found to be significantly higher in the patient group (the p values were 0.0002 and 0.003, respectively).

Conclusions

The fact that the CC genotype was found to be significantly higher in the patient group compared to the control group (p = 0.0002) and that it had a statistically significantly higher OR value (OR, 95% CI = 4.16, 1.91–9.05) suggests that the C allele may recessively predispose to MS for this polymorphism. These results suggest for the first time that the NCOA5 gene may have an effect on the occurrence of MS through different molecular pathways, which are discussed in the manuscript.

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Data Availability

Detailed data on the findings of this study are obviously not available due to sensitivity and are available from the corresponding author upon reasonable request.

Abbreviations

CIA:

Coactivator Independent of AF2

CNS:

Central Nervous System

CSF:

Cerebrospinal Fluid

EAE:

Experimental Autoimmune Encephalomyelitis

EDSS:

Expanded Disability Status Scale

GWAS:

Genome-Wide Association Studies

HCC:

Hepatic Cell Carcinoma

HLA:

Human Leukocyte Antigen

IL-6:

Interleukin-6

IMSGC:

International Multiple Sclerosis Genetics Consortium

MHC:

Major Histocompatibility Complex

MS:

Multiple Sclerosis

MSSS:

Multiple Sclerosis Severity Scale

NCOA5:

The Nuclear Receptor Coactivator 5

NO:

Neuromyelitis Optica

NR1D2:

Nuclear Receptor Subfamily 1 Group D Member 2

RA:

Rheumatoid Arthritis

RORA:

Retinoic Acid Receptor-Associated Orphan Receptor Alpha

RT-PCR:

Real-Time Polymerase Chain Reaction

SNP:

Single Nucleotide Polymorphism

SPSS:

Statistical Package for the Social Sciences

T1D:

Type I Diabetes

T2D:

Type 2 Diabetes

TAGAP:

T Cell Activation RhoGTPase Activating Protein

TNF:

Tumor Necrosis Facto

TYK2:

Tyrosine Kinase 2

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Acknowledgements

This study was supported by Tokat Gaziosmanpasa University Scientific Research Projects Commission. (Project No: 2015/67).

We gracefully thank the patients and the medical staff of the Tokat Gaziosmanpasa University Research Hospital for their support and contribution to the study.

Funding

This study was supported by Tokat Gaziosmanpasa University Scientific Research Projects Commission [Project No: 2015/67].

Author information

Authors and Affiliations

  1. Faculty of Medicine, Department of Medical Biology, Tokat Gaziosmanpasa University, Tokat, Turkey

    Husniye Rustemoglu & Sema Atasever

  2. Faculty of Medicine, Department of Medical Pharmacology, Aksaray University, Aksaray, Turkey

    Erdem Arslan

  3. Faculty of Medicine, Department of Neurology, Tokat Gaziosmanpasa University, Tokat, Turkey

    Betul Cevik

  4. Faculty of Medicine, Department of Physiology, Aksaray University, Aksaray, Turkey

    Filiz Taspinar

  5. Faculty of Medicine, Department of Medical Biology, Aksaray University, Bahcesaray Mah. 170. Cad. No:19, Aksaray, 68100, Turkey

    Ahmet Bülent Turhan & Aydin Rustemoglu

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  1. Husniye Rustemoglu
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Aydin Rustemoglu, Sema Atasever, Betul Cevik and Husniye Rustemoglu; data analysis, evaluation and article writing were performed by Husniye Rustemoglu, Erdem Arslan, Ahmet Bulent Turhan, Filiz Taspinar and Aydin Rustemoglu. The first draft of the manuscript was written by Husniye Rustemoglu and Erdem Arslan. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Aydin Rustemoglu.

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Conflict of interest

The authors declare no competing interest. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence.

Ethical approval

This study was performed in line with the principles of the Declaration of Helsinki. The study was started after the approval of Tokat Gaziosmanpaşa University Faculty of Medicine Ethics Committee (15-KAEK-016).

Informed consent

Informed consent was obtained from all individual participants included in the study.

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The authors confirm that the MS patients and control subjects included in the study gave voluntary consent for the publication of study data and clinical data.

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Rustemoglu, H., Arslan, E., Atasever, S. et al. Could NCOA5 a novel candidate gene for multiple sclerosis susceptibility?. Mol Biol Rep 50, 9335–9341 (2023). https://doi.org/10.1007/s11033-023-08830-6

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