Genetic Variability in Vascular Endothelial Growth Factor A and Risk of Psoriasis
Katerina Apostolaki¹, Martha-Spyridoula Katsarou¹, Annia Tsolakou¹, Polytimi Sidiropoulou¹,², Maria Papasavva³, Natalia Rompoti², Maria Sifaki¹, Alexandros Stratigos², Nikolaos Drakoulis¹ and Electra Nicolaidou²
1Research Group of Clinical Pharmacology and Pharmacogenomics, Faculty of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Athens, Greece
21st Dept of Dermatology-Venereology, Medical School, National and Kapodistrian University of Athens, “A. Sygros” Hospital, Athens, Greece
³Department of Pharmacy, School of Health Sciences, Frederick University, Nicosia, Cyprus
Psoriasis is a chronic autoimmune disease characterized by epidermal hyperplasia, dermal inflammation and neoangiogenesis. Vascular endothelial growth factor A (VEGFA), a key regulator of angiogenesis, is overexpressed in psoriatic skin. Although certain VEGFA gene polymorphisms have been associated with autoimmune conditions, their role in psoriasis remains unclear, particularly among Caucasian populations. To investigate the association of three VEGFA promoter polymorphisms –rs699947 (−2578 C/A), rs2010963 (+405 G/C) and rs1570360 (-1154 G/A)– with psoriasis susceptibility, age at onset and the Koebner phenomenon in a Southeastern European Caucasian population. A total of 194 psoriasis patients and 476 ethnicity-matched general population controls were genotyped using qPCR and melting curve analysis. Genotypic and allelic distributions were evaluated under five genetic models. Associations were assessed using odds ratios (ORs) with 95% confidence intervals (CIs). The rs699947 C allele was significantly associated with increased risk of psoriasis (OR = 1.52, p = 0.001), particularly under the additive model. rs2010963 and rs1570360 polymorphisms showed no association with disease susceptibility. Within the psoriasis cohort, the rs699947 C allele and CC genotype, as well as the rs2010963 CC genotype were more frequent in patients with late-onset disease. However, the A allele and AA genotype of rs1570360 were more prevalent among patients with early psoriasis onset. Additionally, the rs2010963 C allele and GC genotype were underrepresented in patients exhibiting the Koebner phenomenon (OR=0.61, p < 0.05), suggesting a protective effect. These findings suggest a role for rs699947 in susceptibility to and age at onset of psoriasis, and for rs2010963 and rs1570360 in age onset and modulating risk for trauma-induced lesion development. These VEGFA promoter gene variants may hold potential as molecular biomarkers for genetic risk stratification and personalized management in psoriasis.