Tumor necrosis factor gene polymorphisms are associated with systemic lupus erythematosus susceptibility or lupus nephri
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ORIGINAL ARTICLE
Tumor necrosis factor gene polymorphisms are associated with systemic lupus erythematosus susceptibility or lupus nephritis in Mexican patients Julian Ramírez-Bello 1,2 & Daniel Cadena-Sandoval 1,3 & Jorge Flavio Mendoza-Rincón 4 & Rosa Elda Barbosa-Cobos 5 & Fausto Sánchez-Muñoz 6 & Luis M Amezcua-Guerra 6 & Mónica Sierra-Martínez 7 & Silvia Jiménez-Morales 8
# Springer Science+Business Media, LLC, part of Springer Nature 2018
Abstract The TNF -238G/A (rs361525) and -308G/A (rs1800629) polymorphisms have consistently been associated with systemic lupus erythematosus (SLE) in several populations; however, these findings have not been verified in all populations. Here, we aimed to examine whether the TNF -238G/A, -308G/A, -376G/A (rs1800750), and -1031T/C (rs1799964) polymorphisms confer SLE or lupus nephritis (LN) susceptibility in a Mexican population. Our study included 442 patients with SLE and 495 controls. For genotyping, we used the TaqMan 5′ allele discrimination assay. The TNF -238G/A and -1031T/C polymorphisms were associated with SLE susceptibility (odds ratio (OR) 2.1, p = 0.0005 and OR 1.4, p = 0.003, respectively). Gender stratification showed a strong association between TNF -238G/A and SLE in women (OR 2.2, p = 0.00006), while TNF -1031T/C had an OR of 1.5 (p = 0.007). With regard to the TNF -376G/A polymorphism, this also showed association with SLE susceptibility (OR 1.95, p = 0.036) and LN (OR 3.5, p = 0.01). In conclusion, our study provides the first demonstration of association between the TNF -376G/A polymorphism and SLE and LN susceptibility. In addition, our study is the second documenting an association of TNF -1031T/C with SLE susceptibility. We also observed a strong association between TNF -238G/A and SLE susceptibility. The TNF 308G/A polymorphism was not associated with SLE or LN. Keywords Systemic lupus erythematosus . Rheumatoid arthritis . Tumor necrosis factor . Susceptibility
Introduction The tumor necrosis factor (TNF) gene encodes the TNF cytokine, a multifunctional protein and one of the major regulators of inflammation that is involved in different normal immunological processes, including the optimal defense against pathogens, germinal center formation, resolution of inflammation, induction of tissue repair, apoptosis, proliferation, and
* Julian Ramírez-Bello [email protected] 1
Unidad de Investigación en Investigación en Enfermedades Metabólicas y Endócrinas, Hospital Juárez de México, Mexico City, Mexico
necrosis [1, 2]. Moreover, this same cytokine plays an important role in pathological processes, e.g., it induces its own secretion in macrophages, orchestrates the tissue recruitment of immune cells, promotes tissue destruction, and stimulates the synthesis of inflammatory cytokines, chemokines, and different cell survival factors [1–3]. Additionally, TNF is involved in acute/chronic inflammation and has been associated with several inflammatory and autoimmune diseases (ADs)
4
Laboratorio de Oncología Molecular, Unidad de Diferencia
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