Institute of Genetics and Biophysics A. Buzzati-Traverso, CNR, Naples, Italy.
PLoS One. 2012;7(8):e42537. doi: 10.1371/journal.pone.0042537. Epub 2012 Aug 20.
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.
胎盘生长因子（PGF）是血管生成的关键分子。多项研究表明，PGF 主要在病理条件下（例如：缺血、肿瘤形成、心血管疾病和炎症过程）发挥重要作用，提示其可用作潜在的治疗剂。然而，迄今为止，尚无关于 PGF 变异的遗传学信息。此外，尽管已经研究了环境因素（例如：吸烟）对血管生成的影响，但迄今为止尚无关于这些因素对 PGF 水平影响的报道。在这里，我们首次在两个关注非遗传风险因素的队列中研究了 PGF 的变异性：一个来自意大利南部 Cilento 地区两个孤立村庄的研究样本（N=871）和一个来自丹麦普通人群的复制样本（N=1812）。我们发现两个队列之间的 PGF 平均水平存在显著差异。然而，在两个样本中，我们观察到 PGF 水平与年龄和性别之间存在很强的相关性，男性的 PGF 水平明显高于女性。有趣的是，吸烟也被发现会影响两个群体的这种特征，尽管方式不同。然后，我们专注于遗传风险因素。研究了位于 PGF 基因中的五个单核苷酸多态性（SNP）与蛋白质血浆水平之间的关联。两个多态性（rs11850328 和 rs2268614）与 Cilento 样本中的 PGF 血浆水平相关，这些关联在丹麦样本中得到了强烈复制。这些结果首次支持了存在影响 PGF 血浆变异性的遗传和环境因素的假设。
