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PAI-1 mRNA expression and plasma level in rheumatoid arthritis: relationship with 4G/5G PAI-1 polymorphism

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Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting the synovial membrane, cartilage and bone. PAI-1 is a key regulator of the fibrinolytic system through which plasminogen is converted to plasmin. The plasmin activates the matrix metalloproteinase system, which is closely related with the joint damage and bone destruction in RA. The aim of this study was to investigate the relationship between 4G/5G PAI-1 polymorphism with mRNA expression and PAI-1 plasma protein levels in RA patients. 113 RA patients and 123 healthy subjects (HS) were included in the study. The 4G/5G PAI-1 polymorphism was determined by polymerase chain reaction–restriction fragment length polymorphism method; the PAI-1 mRNA expression was determined by real-time PCR; and the soluble PAI-1 (sPAI-1) levels were quantified using an ELISA kit. No significant differences in the genotype and allele frequencies of 4G/5G PAI-1 polymorphism were found between RA patients and HS. However, the 5G/5G genotype was the most frequent in both studied groups: RA (42%) and HS (44%). PAI-1 mRNA expression was slightly increased (0.67 fold) in RA patients with respect to HS (P = 0.0001). In addition, in RA patients, the 4G/4G genotype carriers showed increased PAI-1 mRNA expression (3.82 fold) versus 4G/5G and 5G/5G genotypes (P = 0.0001), whereas the sPAI-1 plasma levels did not show significant differences. Our results indicate that the 4G/5G PAI-1 polymorphism is not a marker of susceptibility in the Western Mexico. However, the 4G/4G genotype is associated with high PAI-1 mRNA expression but not with the sPAI-1 levels in RA patients.

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Acknowledgments

This work was supported by Grant No. 69235 to JFMV of the CONACYT (Fondo Sectorial Secretaria 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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The authors declare that they do not have any conflict of interest.

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Authors and Affiliations

  1. 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, Jalisco, Mexico

    José Francisco Muñoz-Valle, Sandra Luz Ruiz-Quezada, Edith Oregón-Romero & Rosa Elena Navarro-Hernández

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

    Eduardo Castañeda-Saucedo, Ulises De la Cruz-Mosso, Berenice Illades-Aguiar, Marco Antonio Leyva-Vázquez, Natividad Castro-Alarcón & Isela Parra-Rojas

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  1. José Francisco Muñoz-Valle
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  2. Sandra Luz Ruiz-Quezada
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  3. Edith Oregón-Romero
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  7. Berenice Illades-Aguiar
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  8. Marco Antonio Leyva-Vázquez
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  9. Natividad Castro-Alarcón
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  10. Isela Parra-Rojas
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Correspondence to José Francisco Muñoz-Valle.

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Muñoz-Valle, J.F., Ruiz-Quezada, S.L., Oregón-Romero, E. et al. PAI-1 mRNA expression and plasma level in rheumatoid arthritis: relationship with 4G/5G PAI-1 polymorphism. Rheumatol Int 32, 3951–3956 (2012). https://doi.org/10.1007/s00296-011-2279-y

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  • DOI: https://doi.org/10.1007/s00296-011-2279-y

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