Abstract
We assessed whether the −844 G/A polymorphism and mRNA expression of plasminogen activator inhibitor 1 (PAI-1) gene are associated with rheumatoid arthritis (RA). Demographic data, hematological, biochemical parameters, disease activity–disability indexes, −844 G/A genotypes and mRNA expression levels of the PAI-1 gene were determined in 50 RA patients and 50 healthy subjects (HS). Non-significant differences in genotype and allele frequencies related to −844 G/A polymorphism in RA versus HS, were found. High mRNA expression of the PAI-1 gene, was demonstrated in RA versus HS (P < 0.05). In addition, A/A genotype carriers showed increase of PAI-1 mRNA expression (3.1-fold) respect to G/G and G/A genotypes in RA patients (P < 0.05). Our finding suggest an association of A/A −844 PAI-1 genotype with high PAI-1 mRNA expression in RA patients.
Similar content being viewed by others
References
Firestein GS (2003) Evolving concepts of rheumatoid arthritis. Nature 423:356–361
Firestein GS (2005) Immunologic mechanisms in the pathogenesis of rheumatoid arthritis. J Clin Rheumatol 11:S39–S44
Pope RM (2002) Apoptosis as a therapeutic tool in rheumatoid arthritis. Nat Rev Immunol 2:1–9
Arend WP (2001) Physiology of cytokine pathways in rheumatoid arthritis. Arthritis Care Res 45:101–106
Gils A, Declerck PJ (2004) Plasminogen activator inhibitor-1. Curr Med Chem 11:2323–2334
Agirbasli M (2005) Pivotal role of plasminogen-activator inhibitor 1 in vascular disease. Int J Clin Pract 59:102–106
Busso N, Péclat V, So A, Sappino AP (1997) Plasminogen activation in synovial tissues: differences between normal, osteoarthritis, and rheumatoid arthritis joints. Ann Rheum Dis 56:550–557
Ruiz-Quezada S, Vázquez-Del Mercado M, Parra-Rojas I, Rangel-Villalobos H, Best-Aguilera C, Sánchez-Orozco LV, Muñoz-Valle JF (2004) Genotype and allele frequency of PAI-1 promoter polymorphism in healthy subjects from the west of Mexico. Association with biochemical and hematological parameters. Ann Genet 47:155–162
Grubic N, Stegnar M, Peternel P, Kaider A, Binder BR (1996) A novel G/A and the 4G/5G polymorphism within the promoter of the plasminogen activator inhibitor-1 gene in patients with deep vein thrombosis. Thromb Res 84:431–443
Henry M, Chomiki N, Scarabin PY, Alessi MC, Peiretti F, Arveiler D, Ferrieres J, Evans A, Amouyel P, Poirier O, Cambien F, Juhan-Vague I (1997) Five frequent polymorphisms of the PAI-1 gene lack of association between genotypes, PAI activity, and triglyceride levels in a healthy population. Arterioscler Thromb Vasc Biol 17:851–858
Morange PE, Henry M, Tregouët D, Granel B, Aillaud MF, Alessi MC, Juhan-Vague I (2000) The A −844G polymorphism in the PAI-1 gene is associated with a higher risk of venous thrombosis in factor V Leiden carriers. Arterioscler Thromb Vasc Biol 20:1387–1391
Lopes C, Dina C, Durand E, Froguel P (2003) PAI-1 polymorphisms modulate phenotypes associated with the metabolic syndrome in obese and diabetic Caucasian population. Diabetologia 46:1284–1290
Henry M, Tregouët DA, Alessi MC, Aillaud MF, Visvikis S, Siest G, Tiret L, Juhan-Vague I (1998) Metabolic determinations are much more important than genetic polymorphisms in determining the PAI-1 activity and antigen plasma concentrations. A family study with part of the Stanislas cohort. Arterioscler Thromb Vasc Biol 18:84–91
Lu F, Hong J, Kening S, Cuili Z, Jingxia S, Yonglin H (2001) Relationship between gene polymorphism of the PAI-1 promoter and myocardial infarction. Chin Med J 114:266–269
Haselbauer A, Haberbosch W, Tillmanns H, Gardemann A (2002) The impact of the PAI-1 A(−844)G promoter polymorphism on the risk and extent of coronary heart disease. Thromb Haemost 88:697–698
Cardiel MH, Abello-Banfi M, Ruiz-Mercado R, Alarcon-Segovia D (1993) How to measure health status in rheumatoid arthritis in non-English speaking patients: validation of a Spanish version of the Health Assessment Questionnaire Disability Index (Spanish HAQ-DI). Clin Exp Rheumatol 11:117–121
Prevoo ML, van ‘t Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL (1995) Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 38:44–48
Miller SA, Dykes DD, Polesky HF (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16:1215
Vázquez-Del Mercado M, Delgado-Rizo V, Muñoz-Valle JF, Orozco-Alcalá J, Volk HD, Armendáriz-Borunda J (1999) Expression of interleukin-1β, tumor necrosis factor α, interleukins−6, −10 and −4, and metalloproteases by freshly isolated mononuclear cells from early never-treated and non-acute treated rheumatoid artritis patients. Clin Exp Rheumatol 17:575–583
Muñoz-Valle JF, Vázquez-Del Mercado M, García-Iglesias T, Orozco-Barocio G, Bernard-Medina G, Martínez-Bonilla G, Bastidas-Ramírez BE, Navarro AD, Bueno M, Martínez-López E, Best-Aguilera CR, Kamachi M, Armendáriz-Borunda J (2003) TH1/TH2 cytokine profile, metalloprotease-9 activity and hormonal status in pregnant rheumatoid arthritis and systemic lupus erythematosus patients. Clin Exp Immunol 131:377–384
Fabbro D, Délia AV, Spizzo R, Driul L, Barillari G, Di Loreto C, Marcheson D (2003) Association between plasminogen activator inhibitor 1 gene polymorphisms and preeclampsia. Gynecol Obstet Invest 56:17–22
Smolarz B, Blasiak J, Kulig A, Romanowicz-Makowska H, Ulanska J, Pander B, Szewczyk T (2001) Plasminogen activator inhibitor 1 (PAI-1) levels and gene promoter polymorphisms in subjects with colorectal cancer. J Exp Clin Cancer Res 20:247–252
Keene JD (2001) Ribonucleoprotein infrastructure regulating the flow of genetic information between the genome and the proteome. Proc Natl Acad Sci USA 98:7018–7024
Choy EH, Panayi GS (2001) Cytokine pathways and joint inflammation in rheumatoid arthritis. N Engl J Med 344:907–916
Svenson KLG, Lithell H, Hallgren R, Vessby B (1987) Serum lipoprotein in active rheumatoid arthritis and other chronic inflammatory arthritides: I. Effects of anti-inflammatory and disease-modifying drug treatment. Arch Intern Med 147:1917–1920
Wallace DJ (1994) Antimalarial agents and lupus. In systemic lupus erythematosus. Dis Clin North Am 20:243–263
Nodis HN, Quismorio FP, Wickham E, Blankenhorn DH (1993) The lipid, lipoprotein, and apolipoprotein effects of hydroxyl-chloroquine in patients with systemic lupus erythematosus. J Rheumatol 20:661–665
Acknowledgments
This work was supported by grant no. 45703-M to JFMV of the National Council of Science and Technology (CONACyT, México-Universidad de Guadalajara). Preliminary results were presented in the Annual European Congress of Rheumatology, EULAR 2006 in Amsterdam, The Netherlands.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Torres-Carrillo, N.M., Torres-Carrillo, N., Vázquez-Del Mercado, M. et al. The −844 G/A PAI-1 polymorphism is associated with mRNA expression in rheumatoid arthritis. Rheumatol Int 28, 355–360 (2008). https://doi.org/10.1007/s00296-007-0453-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00296-007-0453-z