Genetic interaction between placenta growth factor (PGF) and vascular endothelial growth factor A (VEGFA) in psoriasis.

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 age 40 years). Studies have suggested that expression of placenta growth factor (PGF) is also up-regulated in cutaneous inflammation and that VEGFA-mediated angiogenesis may be dependent on the simultaneous presence of PGF within the skin. To elucidate the biological importance of PGF in psoriasis we investigated whether two commonly occurring PGF polymorphisms were associated with early-onset psoriasis and the genetic interaction between VEGFA and PGF in psoriasis. We observed significant association between rs2268614 TT and rs2268615 AA genotypes of PGF and early-onset psoriasis (p=0.04). 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=0.028). We identified that VEGFA genotype influences PGF expression (p=0.001) and that mean plasma levels of PGF are lower in patients with severe psoriasis compared to those with mild-moderate disease (p=0.04). Our observed genetic interaction between PGF and VEGFA appears relevant to psoriasis - a disease with an angiogenic basis - and may influence development of an anti-angiogenic approach to treatment.