Modulation of Biomarkers Associated With Lymphangiogenesis and Cardiovascular Risk by Polymorphic Genetic Variants of Aquaporins and Heparanase in Psoriasis

Abstract

Objective:Psoriasis is a chronic inflammatory disease associated with cardiovascular risk factors. Aquaporins(AQP) are a family of channels, which can transport: water, urea, hydrogen peroxide and/or glycerol, essential for redox signalling and metabolic skin homeostasis.Heparanase(HPSE) is an endo--glucuronidase that cleaves heparan sulfate chains of proteoglycans from the extracellular matrix(ECM), an essential step in the neovascularization and cell growth process.Vascular endothelial growth factor-C(VEGF-C) is an important growth factor regulating lymphatic neovascularization and pathological processes associated with sodium accumulation in ECM in the skin. The VEGF soluble receptors(s-flt1) are decoy receptors present in endothelial cells, hematopoietic stem cells, monocytes, macrophages, and platelets.This study aims to evaluate the impact of AQP3, AQP7 and HPSE genetic polymorphisms in biomarkers related to cardiovascular risk in patients with psoriasis and their clinical severity determined by Psoriasis Area and Severity Index(PASI).Design and method:Sixty-three psoriasis patients with a mean age of 52.50 ± 12.81years. Sociodemographic, hemodynamic and routine blood laboratory data were collected. Biochemical parameters were determined in serum according to standardized methods. Genetic polymorphisms were determined by endpoint analysis and s-flt1 and VEGF-C by ELISA. Patients were stratified based on PASI:< 5(G1) and > or equal to 5(G2). For statistical analysis, SPSS program was used with a p-value < 0.05.Results:Comparing the genotypic and allelic frequencies of the studied polymorphisms, no differences were found between G1 and G2.In general, patients with genotype AA of AQP3 had higher levels of s-flt1(p = 0.005) and VEGF-C(p = 0.048). For AQP7, genotype TT was associated with higher levels of mean platelet volume(p = 0.049) and lower levels of creatinine(Cr)(p = 0.023).Elevated levels of neutrophils(N)(p = 0.017) and potassium(p = 0.001) was observed in genotype AA of HPSE.For G1 was observed an increased level of: s-flt1(p = 0.022) and VEGF-C(p = 0.044) associated with genotype AA of AQP3; Cr in allele C of AQP7(p = 0.018), N in genotype CC of AQP7(p = 0.017). For G2 was observed: higher levels of leucocytes in allele C of AQP3(p = 0.016) and angiotensin-converting enzyme activity(ACE1) in allele T of AQP7(p = 0.033).Conclusions:AQP3, AQP7 and HPSE polymorphisms appear to modulate some biochemical parameters relevant to lymphangiogenesis associated with cardiovascular risk in a sample of patients with psoriasis.