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Tumor necrosis factor beta (TNF-β) NcoI polymorphism is associated with multiple sclerosis in Caucasian patients from Southern Brazil independently from HLA-DRB1

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Abstract

This study evaluated the association of tumor necrosis factor beta (TNF-β) NcoI polymorphism with the presence of multiple sclerosis (MS), disability, and HLA-DRB1 alleles in 208 Brazilian MS patients. As controls, 147 healthy individuals were included. The disability was evaluated at baseline and 5-year follow-up using the Expanded Disability Status Scale (EDSS). The TNF-β genotypes were determined using PCR and restriction fragment length polymorphism and serum TNF-α level was determined using enzyme-linked immunosorbent assay. Among the MS patients, 166 (79.8 %) were white, 39 (18.7 %) were brown, and three (1.4 %) were Asian descents (those were excluded from the further analysis). Among the 205 MS patients, 149 (72.6 %) presented remitting–relapsing MS. The baseline and 5-year follow-up EDSS ranged from 0.0 to 3.0 and from 1.0 to 5.7, respectively. The TNFB2/B2 genotype was associated with the presence of MS among the white patients (p = 0.0443). Brown patients presented higher disability (p = 0.0234) and higher TNF-α levels (p = 0.0463) than white patients. White and brown patients carrying TNFB2/B2 genotype exhibited higher TNF-α levels (p = 0.0354 and p = 0.0309, respectively) than those with other geotypes. Association between TNF-β NcoI genotypes and HLA-DRB1 alleles was not observed among the MS patients (p > 0.05). Taken together, TNFB2 allele was associated with the presence of MS independently of HLA-DRB1 in white patients and the TNFB2/B2 genotype was associated with increased TNF-α levels in white and brown patients, which could be an important genetic factor candidate for the susceptibility and pathogenesis of MS.

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Acknowledgments

The study was supported by grants from Coordination for the Improvement of Higher Level of Education Personnel (CAPES) of Brazilian Ministry of Education; Institutional Program for Scientific Initiation Scholarship (PIBIC) of the National Council for Scientific and Technological Development (CNPq), State University of Londrina (PROPPG), and Bayer HealthCare. We thank the University Hospital of State University of Londrina and HUTec Foundation for technical and administrative supports.

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All the authors declare that there is no conflict of interest.

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Authors and Affiliations

  1. Health Sciences Postgraduate Program, Health Sciences Center, State University of Londrina, Londrina, Paraná, Brazil

    A. P. Kallaur, S. R. Oliveira, J. Lopes & Daniele Frizon Alfieri

  2. Department of Pathology, Clinical Analysis, and Toxicology, Health Sciences Center, State University of Londrina, Av. Robert Koch, 60, CEP 86.038-440, Londrina, Paraná, Brazil

    A. N. C. Simão, E. R. D. de Almeida, H. K. Morimoto, D. R. Kaimen-Maciel & E. M. V. Reiche

  3. Outpatient Clinic for Multiple Sclerosis, University Hospital, State University of Londrina, Londrina, Paraná, Brazil

    L. M. Pelegrino, W. L. C. J. de Pereira & R. M. Andrade

  4. Department of Clinical Analysis, Laboratory of Immunogenetics, State University of Maringá, Maringá, Paraná, Brazil

    S. D. Borelli

  5. Department of Pathological Sciences, Biological Sciences Center, State University of Londrina, Londrina, Paraná, Brazil

    M. A. E. Watanabe

  6. Department of Clinical Medicine, Health Sciences Center, State University of Londrina, Londrina, Paraná, Brazil

    D. R. Kaimen-Maciel

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  1. A. P. Kallaur
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  2. S. R. Oliveira
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  3. A. N. C. Simão
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  4. E. R. D. de Almeida
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  12. M. A. E. Watanabe
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  14. E. M. V. Reiche
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Kallaur, A.P., Oliveira, S.R., Simão, A.N.C. et al. Tumor necrosis factor beta (TNF-β) NcoI polymorphism is associated with multiple sclerosis in Caucasian patients from Southern Brazil independently from HLA-DRB1 . J Mol Neurosci 53, 211–221 (2014). https://doi.org/10.1007/s12031-014-0287-6

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