Genetic and environmental determinants of circulating levels of angiogenin in community-based sample

Background: Measurement of angiogenin in plasma provides important prognostic and diagnostic information in variety of malignancies and may even correlate with cancer's progression. Nevertheless, nowadays, specific physiological mechanisms of this protein action as well as major factors regulating its circulating levels normally and in pathology are still poorly understood. The main objectives of this study were to examine the contribution of a number of endogenous factors, such as sex, age, body size and genetic effects on the production of angiogenin in apparently healthy individuals, and to assess the correlations in circulating levels between angiogenin and other molecules involved in angiogenesis. Methods: The plasma levels of angiogenin and each of the additional cytokines [interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β), macrophage-colony stimulating factor (M-CSF), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), soluble intercellular adhesion molecule-1 (sICAM)] were determined by enzyme-linked immunoassay in a large family based sample. Results: Angiogenin levels were significantly higher in man than in women (360.64 104.04 ng/ml vs. 322.15 100.34 ng/ml, P < 0.01) and significantly correlated with age (P < 0.01) in both sexes. Genetic analysis showed that adjusted for potential covariates, 37.4 7.1% of angiogenin variation was attributable to putative genetic factors. The results of our study revealed that angiogenin concentrations were positively and significantly (P < 0.05) associated with sICAM, IL-6, TNF-α and M-CSF levels in the female cohort. Conclusions: Our data provide reliable evidence for the substantial role of genetic factors in the determination of the phenotypic variability of angiogenin plasma levels. These findings of our study, including circulating angiogenin reference limits in healthy population and its correlation with angiogenic cytokines, may be of importance in determination of early stages of pathological angiogenesis.