Abstract
Systemic sclerosis (SSc) is a systemic connective tissue disease characterized by excessive fibrosis, vascular injury, autoimmunity and inflammation. P-selectin glycoprotein ligand-1 (PSGL-1) expressed on leukocytes and microparticles derived from myeloid cells is major counter-receptor for P-selectin. P-selectin and PSGL-1 crosslinking mediates interaction among leukocytes, platelets and endothelial cells during thrombosis, inflammation, and angiogenesis.It has been postulated that the recently defined “variable number tandem repeats” (VNTR) polymorphisms of the mucin-like region of PSGL-1 might effect the adhesion function by changing the interaction between P-selectin and PSGL-1. We aimed to investigate the distribution of PSGL-1 VNTR polymorphisms in SSc and to compare with the healthy controls in order to study the role of these polymorphisms in the pathogenesis of SSc and its complications. One hundred and fourteen SSc patients (102 women, 12 men) who fulfilled 1980 ACR preliminary criteria and 203 unrelated healthy controls (98 women, 105 men) were studied. Demographic and clinical characteristics of the patients were recorded by using a standart form. The study was approved by the local ethical committee and subjects signed informed consent documents. PSGL-1 polymorphisms were determined with PCR method (1). 4 genotypes were identified after genotyping according to bands in gel electrophoresis (AA, AB, BB, AC). Cumulative frequencies of A, B and C alleles in SSc were 77.2%, 21.5% and 1.3%, respectively and 82.4%, 15.4% and 2.2% in the control group. The AA, AB, BB and AC genotype frequencies were 59.6%, 32.5%, 5.3% and 2.6% in SSc and 70%, 21.2%, 4.9% and 3.9% in control group. 37 of 114 SSc patients were carrying the AB genotype (32.5% vs 21.2%, OR=1.79, 95% CI 1.07–3.0, p=0.027). B allele carriers were 37.7% in SSc and 26.1% in control group (OR=1.71, 95% CI 1.04–2.80, p=0.031). When two major disease subsets were considered, AB genotype was found to be more frequent in patients with limited cutaneous involvement (lSSc) (34.8% vs 21.2%, OR=1.99, 95% CI 1.084–3.65, p=0.025). However, the frequency of AB genotype in diffuse systemic sclerosis (dSSc) was similar to that of control group (p=0.75). Similarly, B allele carriers were more frequent in lSSc (40.9% vs 26.1%, OR=1.96, 95% CI 1.1–3.5, p=0.022). When the clinical and laboratory characteristics of patients were taken into consideration, AB genotype was significantly less frequent in anti-Scl70 positive patients compared to anti-Scl70 negative patients (21.8% vs. 42.9%, OR=0.37, 95% CI 0.16–0.85, p=0.018). Likewise, B allele carriers were less frequent in anti-Scl70 positive patients (29.4% vs. 49.1%, OR=0.43, 95% CI 0.19–0.96, p=0.038). The AB genotype was increased in patients with arthritis compared to patients with no arthritis (77.8% vs. 28.3%, OR=8.87, 95% CI 1.73–45.35, p=0.002). PSGL-1 VNTR polymorphisms were distributed significantly different in SSc and healthy controls when clinical subsets of SSc were analysed seperately. The AB genotype and B allele were significantly more frequent in lSSc. This finding was also supported by the low frequency of AB genotype and B allele in anti-Scl70 positive patients, which is more common in dSSc. PSGL-1 VNTR polymorphisms might play a role in the pathogenesis of lSSc by modifying leukocyte, platelet and endothelial cell interactions. Further research is needed to confirm the relationship with AB genotype and arthritis in SSc patients.
Expression of Microrna-195 Increased Significantly in Patients with Methamphetamine Abuse Disorder
