Placental
Growth Factor (
PGF) is a key molecule in angiogenesis. Several studies have revealed an important role of
PGF primarily in pathological conditions (e.g.: ischaemia, tumour formation,
cardiovascular diseases and inflammatory processes) suggesting its use as a potential therapeutic agent. However, to date, no information is available regarding the genetics of
PGF variability. Furthermore, even though the effect of environmental factors (e.g.: cigarette smoking) on angiogenesis has been explored, no data on the influence of these factors on
PGF levels have been reported so far. Here we have first investigated
PGF variability in two cohorts focusing on non-genetic risk factors: a study sample from two isolated villages in the Cilento region, South Italy (N=871) and a replication sample from the general Danish population (N=1,812). A significant difference in
PGF mean levels was found between the two cohorts. However, in both samples, we observed a strong correlation of
PGF levels with ageing and sex, men displaying
PGF levels significantly higher than women. Interestingly, smoking was also found to influence the trait in the two populations, although differently. We have then focused on genetic risk factors. The association between five single nucleotide polymorphisms (SNPs) located in the
PGF gene and the plasma levels of the
protein was investigated. Two polymorphisms (rs11850328 and rs2268614) were associated with the
PGF plasma levels in the Cilento sample and these associations were strongly replicated in the Danish sample. These results, for the first time, support the hypothesis of the presence of genetic and environmental factors influencing
PGF plasma variability.