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Single nucleotide variants around the connective tissue growth factor (CTGF/CCN2) gene and their association with multiple sclerosis risk, disability scores, and rate of disease progression

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Abstract

Background

This study aimed to explore the possible association of single nucleotide polymorphisms (SNPs) in the upstream (rs9402373) and downstream regions (rs9399005 and rs12526196) of the gene encoding connective tissue growth factor (CTGF/CCN2) with relapsing–remitting multiple sclerosis (RRMS) risk and clinical parameters including disability scores and rate of disability progression.

Materials and methods

In total, 200 patients with RRMS and 305 controls were genotyped using real-time PCR (rs1252696 C/T and rs9402373 G/C) or PCR–RFLP (rs9399005 C/T) methods. Furthermore, the association between these genotypes and clinical parameters including Expanded Disability Status Scale (EDSS) score, Multiple Sclerosis Severity Score (MSSS), age at onset, duration of disease, duration of treatment, and presence of contrast-enhancing lesions was analyzed.

Results

rs9399005 genotypes TT and CT in the dominant model were significant predictors of RRMS vs. control status by logistic regression analysis (OR = 1.45, 95% CI = 1.01–2.08, P = .04). Moreover, these genotypes for rs9399005 were associated with a MSSS ≥ 2.4 (OR = 3.54, 95% CI = 1.56–8.05, P = .003). In addition, MSSS was lower in patients who had at least one rs12526196C allele than in the corresponding patients with the TT genotype (P = .02).

Conclusion

To our knowledge, this is the first evidence of the involvement of variants around the CTGF gene in MS risk and disability progression.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Code availability

Not applicable.

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Acknowledgements

The authors thank the subjects for their participation in this study.

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Authors and Affiliations

  1. Department of Biomedical Engineering, TOBB University of Economics and Technology, Söğütözü, 06560, Ankara, Turkey

    Birsen Can Demirdöğen, Osman Oğuzhan Kılıç, Elif Naz Karagülle & Latife Mekselina Kalmaz

  2. Neurology Clinic, Ankara City Hospital, Ankara, Turkey

    Semra Mungan

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  1. Birsen Can Demirdöğen
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  2. Osman Oğuzhan Kılıç
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Corresponding author

Correspondence to Birsen Can Demirdöğen.

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Ethical approval

This study protocol was approved by the Ethical Committee of Ankara City Hospital.

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All subjects gave written informed consent.

Conflict of interest

The authors declare no competing interests.

Significance

This study reveals the first evidence of the involvement of single nucleotide polymorphisms around the connective tissue growth factor (CTGF) gene in relapsing–remitting multiple sclerosis (RRMS) risk and disability progression. The downstream variant rs9399005 was associated with RRMS and a higher rate of disability progression reflected by a higher Multiple Sclerosis Severity Score (MSSS). Furthermore, MSSS was significantly lower in patients with at least one rs12526196C allele than in the corresponding patients with the wild-type genotype. These data indicate a role for the variants in the region flanking CTGF gene in RRMS risk and disability progression.

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Can Demirdöğen, B., Kılıç, O.O., Karagülle, E.N. et al. Single nucleotide variants around the connective tissue growth factor (CTGF/CCN2) gene and their association with multiple sclerosis risk, disability scores, and rate of disease progression. Neurol Sci 43, 3867–3877 (2022). https://doi.org/10.1007/s10072-021-05852-5

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