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TNFA -308G>A and -238G>A polymorphisms and risk to systemic sclerosis: impact on TNF-α serum levels, TNFA mRNA expression, and autoantibodies

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Abstract

Systemic sclerosis (SSc) is a rare autoimmune disease with high mortality, characterized by chronic inflammation and fibrosis, which are processes associated with higher serum tumor necrosis factor-α (sTNF-α) levels. TNFA -308G>A and -238G>A polymorphisms have been associated with higher sTNF-α levels. In this study, we genotyped the TNFA -308G>A and -238G>A polymorphisms in 53 SSc patients and 115 unrelated control subjects (CS) from southern Mexico. The TNFA mRNA expression and sTNF-α levels were also quantified by qPCR and enzyme-linked immunosorbent assays, respectively. TNFA -308GA genotype was associated with disease susceptibility according to a codominant genetic model (OR = 3.2, 95% CI 1.05–9.75, p = 0.03), and with higher anti-fibrillarin antibodies (p = 0.01), and higher skin thickening (p = 0.006). TNFA -238GA was not associated with SSc risk. TNFA mRNA expression and sTNF-α levels were similar between SSc patients and CS and were not statistically associated with the TNFA polymorphisms; however, a correlation (rho = 0.362, p = 0.009) between sTNF-α levels with anti-RNA polymerase III antibodies was observed in the SSc patients. In conclusion, the -308G>A polymorphism is a genetic marker of SSc susceptibility in population from southern Mexico, and it is associated with skin thickening and anti-fibrillarin antibodies. In addition, sTNF-α levels correlate positively with the anti-RNA pol III antibodies levels.

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Funding

This work was supported by funding from the PRODEP- SEP Mexico under Grant (No. UDG-PTC-1433) assigned to HBJ and by the University of Guadalajara—Strengthening Research and Postgraduate 2018 under Grant (No. 244159) assigned to MVJF. Part of this work was supported by PROFIDES-SEP for research networks, 2017 (511-6/18-11870).

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Authors and Affiliations

  1. Instituto de Investigación en Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Sierra Mojada 950, Independencia Oriente, 44340, Guadalajara, Jalisco, Mexico

    José Alvaro Lomelí-Nieto, José Francisco Muñoz-Valle, Mariel García-Chagollán & Jorge Hernández-Bello

  2. Instituto Transdisciplinar de Investigación y Servicios, Universidad de Guadalajara, Zapopan, Jalisco, Mexico

    José Alvaro Lomelí-Nieto, José Francisco Muñoz-Valle & Jorge Hernández-Bello

  3. Facultad de Ciencias Químico-Biológicas, Universidad Autónoma de Guerrero, Chilpancingo, Guerrero, Mexico

    Christian Johana Baños-Hernández & Isela Parra-Rojas

  4. Departamento de Medicina Interna/Reumatología, Hospital General de Chilpancingo “Dr. Raymundo Abarca Alarcón”, Chilpancingo de los Bravo, Guerrero, Mexico

    José Eduardo Navarro-Zarza

  5. Laboratorio de Inmunología, Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico

    María Guadalupe Ramírez-Dueñas, Pedro Ernesto Sánchez-Hernández & Andrea Carolina Machado-Sulbaran

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  1. José Alvaro Lomelí-Nieto
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  2. José Francisco Muñoz-Valle
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Correspondence to Jorge Hernández-Bello.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the Local Bioethical Committee at the Hospital General de Chilpancingo “Dr. Raymundo Abarca Alarcón” and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Lomelí-Nieto, J.A., Muñoz-Valle, J.F., Baños-Hernández, C.J. et al. TNFA -308G>A and -238G>A polymorphisms and risk to systemic sclerosis: impact on TNF-α serum levels, TNFA mRNA expression, and autoantibodies. Clin Exp Med 19, 439–447 (2019). https://doi.org/10.1007/s10238-019-00569-4

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