Genetic interaction between placental growth factor and vascular endothelial growth factor A in psoriasis

Abstract

Background: Expression of vascular endothelial growth factor A (VEGFA) is increased in chronic inflammatory skin diseases, including psoriasis, and loci for two VEGFA single nucleotide polymorphisms are associated with early-onset psoriasis (presenting before the age of 40 years). Studies have suggested that expression of placenta growth factor (PGF) is also upregulated in cutaneous inflammation and that VEGFA-mediated angiogenesis may be dependent on the simultaneous presence of PGF within the skin. Aim: To elucidate the biological importance of PGF in psoriasis. Methods: We investigated whether two commonly occurring PGF polymorphisms were associated with early-onset psoriasis and the genetic interaction between VEGFA and PGF in psoriasis. Results: We observed a significant (P = 0.04) association between rs2268614 TT and rs2268615 AA genotypes of PGF and early-onset psoriasis. In addition, genetic complement, comprising the PGF rs2268615 AA genotype and the VEGFA −460 (rs833061) T allele, was significantly associated with the development of early-onset psoriasis (P < 0.03). We identified that the VEGFA genotype influences PGF expression (P = 0.001) and that mean plasma levels of PGF are lower in patients with severe psoriasis compared with those with mild–moderate disease (P = 0.04). Conclusion: Our observed genetic interaction between PGF and VEGFA appears relevant to psoriasis, a disease with an angiogenic basis, and may influence development of an antiangiogenic approach to treatment.