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.
Rheumatol Int. 2012 Dec;32(12):3951-6. doi: 10.1007/s00296-011-2279-y. Epub 2011 Dec 27.
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.
类风湿关节炎（RA）是一种慢性炎症性疾病，影响滑膜、软骨和骨骼。PAI-1 是纤溶系统的关键调节因子，通过该系统将纤溶酶原转化为纤溶酶。纤溶酶激活基质金属蛋白酶系统，该系统与 RA 中的关节损伤和骨破坏密切相关。本研究旨在探讨 4G/5G PAI-1 多态性与 RA 患者 PAI-1mRNA 表达和 PAI-1 血浆蛋白水平之间的关系。研究纳入了 113 例 RA 患者和 123 名健康对照者（HS）。采用聚合酶链反应-限制性片段长度多态性方法检测 4G/5G PAI-1 多态性；实时 PCR 检测 PAI-1 mRNA 表达；ELISA 试剂盒定量检测可溶性 PAI-1（sPAI-1）水平。RA 患者和 HS 之间 4G/5G PAI-1 多态性的基因型和等位基因频率无显著差异。然而，在两个研究组中，5G/5G 基因型最为常见：RA（42%）和 HS（44%）。与 HS 相比，RA 患者的 PAI-1 mRNA 表达略有增加（0.67 倍）（P = 0.0001）。此外，在 RA 患者中，4G/4G 基因型携带者的 PAI-1 mRNA 表达增加（3.82 倍），与 4G/5G 和 5G/5G 基因型相比（P = 0.0001），而 sPAI-1 血浆水平无显著差异。我们的结果表明，4G/5G PAI-1 多态性不是墨西哥西部 RA 的易感性标志物。然而，4G/4G 基因型与 RA 患者高 PAI-1 mRNA 表达相关，但与 sPAI-1 水平无关。
