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High expression of TNF alpha is associated with −308 and −238 TNF alpha polymorphisms in knee osteoarthritis

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Abstract

Knee osteoarthritis (OA) is a common chronic degenerative disease characterized by the loss of articular cartilage components due to an imbalance between extracellular matrix destruction and repair. The proinflammatory cytokines involved in OA, TNFα and IL1β, are considered the major implicated. The aim of this study was to investigate the relationship between TNFα −308 and −238 polymorphisms with messenger RNA (mRNA) and soluble TNFα expression in knee OA patients and healthy subjects (HS). Case–control study involved 50 knee OA patients classified according to 1986 ACR Classification Criteria, as well as 100 HS. The Western Ontario and McMaster Universities Osteoarthritis Index and Lequesne disability index were applied to OA patients. The −308 and −238 polymorphisms were determined by polymerase chain reaction–restriction fragment length polymorphism technique. The TNFα mRNA expression was quantified by real-time PCR using TaqMan method. The sTNFα levels were measured by enzyme-linked immunosorbent assay. The TNFα mRNA expression in knee OA patients was higher than in HS (1.56-fold). In addition, the TNFα mRNA expression was higher in carriers of G allele in the knee OA group for both polymorphisms. The sTNFα levels were increased in G/G versus G/A genotypes in both studied polymorphisms (p < 0.05). However, the TNFα −308 and −238 genotypes did not show statistical differences between groups. The G allele of TNFα −308 and −238 polymorphisms is associated with high mRNA and soluble expression in knee OA patients. However, it is not a marker of susceptibility in Western Mexico. Further studies are necessary to confirm these findings.

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Acknowledgments

This work was supported by Grant No. 69235 to JFMV of the CONACYT (Fondo Sectorial Secretaría de Salud-IMSS-ISSSTE CONACYT, México-Universidad de Guadalajara) and Grant No. 147778 of the Fondo Mixto CONACYT-Gobierno del Estado de Guerrero 2010-01.

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Authors and Affiliations

  1. Grupo de Inmunogenética Funcional, Departamento de Biología Molecular y Genómica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Insurgentes 244-1, Colonia Lomas de Atemajac, C.P. 45178, Zapopan, Guadalajara, Jalisco, Mexico

    José Francisco Muñoz-Valle & Edith Oregón-Romero

  2. Instituto de Investigación en Genética Molecular, Centro Universitario de la Ciénega, Universidad de Guadalajara, Ocotlán, Jalisco, Mexico

    Héctor Rangel-Villalobos

  3. Servicio de Reumatología, OPD Hospital Civil de Guadalajara “Fray Antonio Alcalde”, Guadalajara, Jalisco, Mexico

    Gloria Esther Martínez-Bonilla

  4. Unidad Académica de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Chilpancingo, Guerrero, Mexico

    Eduardo Castañeda-Saucedo, Lorenzo Salgado-Goytia, Marco Antonio Leyva-Vázquez, Berenice Illades-Aguiar, Luz del Carmen Alarcón-Romero, Mónica Espinoza-Rojo & Isela Parra-Rojas

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  1. José Francisco Muñoz-Valle
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Correspondence to José Francisco Muñoz-Valle.

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José Francisco Muñoz-Valle and Edith Oregón-Romero contributed equally to this work.

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Muñoz-Valle, J.F., Oregón-Romero, E., Rangel-Villalobos, H. et al. High expression of TNF alpha is associated with −308 and −238 TNF alpha polymorphisms in knee osteoarthritis. Clin Exp Med 14, 61–67 (2014). https://doi.org/10.1007/s10238-012-0216-3

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