Impact of Plasminogen Activator Inhibitor-1 Serum Levels and the -675 4G/5G Variant in the SERPINE1 Gene on Systemic Sclerosis in a Mexican Population

Abstract

Systemic sclerosis (SSc) is characterized by a complex interplay of vascular damage, inflammation, and fibrosis, affecting the skin and internal organs. Plasminogen activator inhibitor-1 (PAI-1), a protein encoded by the SERPINE1 gene, is a potential biomarker of SSc because it is primarily involved in fibrinolysis and is associated with the severity of some autoimmune diseases. This study aimed to determine the association between SERPINE1 variant -675 4G/5G and soluble PAI-1 (sPAI-1) levels with the clinical characteristics and risk of SSc in a Mexican population. This cross-sectional study included 56 SSc patients and 114 control subjects (CSs). The variant was genotyped via the PCR-RFLP method and the levels of sPAI-1 were determined using enzyme-linked immunosorbent assays (ELISAs). The -675 4G/5G variant was not associated with SSc risk or sPAI-I levels. However, higher sPAI-1 levels were observed in SSc patients than in CSs (p = 0.045); these levels were significantly correlated with age, platelets, glucose, and serum levels of transforming growth factor (TGF)-β1, 2, and 3. The SERPINE1 -675 4G/5G variant did not show any association with SSc risk or sPAI-I levels. However, our study shows a possible alteration of sPAI-1 in this disease, which could be associated with the fibrotic and thrombotic processes in SSc.

Keywords: PAI-1 and fibrotic diseases; PAI-1 in SSc; SERPINE1 4G/5G polymorphism; TGF-β and PAI-1 in SSc; soluble PAI-1 in autoimmune diseases.

Figure 1

Comparison between sPAI-1 levels and different groups. (a) A significant difference was found between the SSc and CSs groups. (b) No significant difference was found between genotypes in SSc patients. (c) A significant difference was found between male and female patients. (d) No significant differences were observed in relation to gender in the control group. Dots represent individual patients, central line indicates median, and box shows interquartile range (IQR). Graphic created with GraphPad Prism v8.0.

Figure 2

Comparison of sPAI-1 with clinical and paraclinical characteristics in SSc patients. (a) A negative correlation was found between sPAI-1 and aging. (b) A positive correlation was found between sPAI-1 and platelets. (c) A negative correlation was found between sPAI-1 and glucose. (d–f) A positive correlation was found between sPAI-1 and sTGF-β1, 2, and 3, individually. Correlation analyses were conducted using Spearman’s correlation coefficient. The red dots represent the individual data points for the two variables being analyzed, while the black line represents the trend line according to Spearman’s correlation coefficien. Graphic created with GraphPad Prism v8.0.

Figure 3

Comparison of PAI-1 levels in SSc patients based on treatment status and disease subtypes. (a) PAI-1 levels in SSc patients comparing those receiving treatment versus those without treatment; (b) PAI-1 levels across different subtypes of SSc, including limited (lcSSc) and diffuse (dcSSc) forms. No significant differences were found. Dots represent individual patients, central line indicates median, and box shows interquartile range (IQR). Graphic created with GraphPad Prism v8.0.