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The -844 G/A PAI-1 polymorphism is associated with mRNA expression in rheumatoid arthritis

Nora Magdalena Torres-Carrillo1, Norma Torres-Carrillo, Mónica Vázquez-Del Mercado

  • 1Instituto de Investigación en Reumatología y del Sistema Músculo Esquelético, Departamento de Biología Molecular y Genómica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Col. Independencia, Guadalajara, Jalisco 44340, Mexico.

Rheumatology International
|September 28, 2007
PubMed

Insights

The plasminogen activator inhibitor 1 (PAI-1) gene shows high mRNA expression in rheumatoid arthritis (RA) patients. The A/A genotype of the -844 PAI-1 polymorphism is linked to this increased expression in RA.

Area of Science:

  • Genetics
  • Immunology
  • Molecular Biology

Background:

  • Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation.
  • Plasminogen activator inhibitor 1 (PAI-1) is a key regulator of fibrinolysis and has been implicated in inflammatory processes.
  • The role of PAI-1 gene polymorphisms and expression in RA pathogenesis requires further investigation.

Purpose of the Study:

  • To investigate the association between the PAI-1 gene -844 G/A polymorphism and mRNA expression levels in rheumatoid arthritis (RA) patients.
  • To compare PAI-1 genetic variations and gene expression between RA patients and healthy subjects (HS).

Main Methods:

  • Genotyping for the PAI-1 -844 G/A polymorphism was performed using standard methods.
  • Quantitative real-time PCR was used to measure PAI-1 mRNA expression levels in peripheral blood samples.
  • Demographic, hematological, biochemical parameters, and disease activity indices were collected and analyzed.

Main Results:

  • No significant differences in genotype or allele frequencies of the PAI-1 -844 G/A polymorphism were observed between RA patients and HS.
  • Significantly higher PAI-1 mRNA expression was found in RA patients compared to HS (P < 0.05).
  • RA patients with the A/A genotype exhibited a 3.1-fold increase in PAI-1 mRNA expression compared to G/G and G/A genotypes (P < 0.05).

Conclusions:

  • The PAI-1 -844 G/A polymorphism itself does not appear to be a significant risk factor for rheumatoid arthritis.
  • Elevated PAI-1 mRNA expression is associated with rheumatoid arthritis.
  • The A/A genotype at the -844 position of the PAI-1 gene is associated with high PAI-1 mRNA expression in RA patients, suggesting a potential role in disease pathophysiology.

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