Angiogenesis-related genes and thalidomide teratogenesis in humans: an approach on genetic variation and review of past in vitro studies

- We reviewed the effect of thalidomide upon angiogenesis in human embryonic cells.
- We investigated variants of susceptibility in Thalidomide Embryopathy (TE) subjects.
- Nitric oxide and β-catenin may be the central molecules affected by thalidomide.
- We could not predict a risk allele or protective one in NOS2, PTGS2 and VEGFA genes.
- Nitric oxide and β-catenin should be further evaluated in thalidomide teratogenesis.

Thalidomide embryopathy (TE) has affected more than 10,000 babies worldwide. The hypothesis of antiangiogenesis as the teratogenic mechanism of thalidomide has been investigated in several experimental models; but, in humans, it has only been accessed by in vitro studies. Here, we hypothesized the effect of thalidomide upon angiogenesis-related molecules or proteins, previously identified in human embryonic cells, through the in silico STRING-tool. We also investigated ten polymorphisms in angiogenesis-related genes in 38 Brazilian TE individuals and 136 non-affected Brazilians. NOS2, PTGS2, and VEGFA polymorphisms were chosen for genotyping. The STRING-tool suggested nitric oxide and β-catenin as the central angiogenesis-related molecules affected by thalidomide's antiangiogenic property. We did not identify a significant difference of allelic, genotypic or haplotypic frequencies between the groups. We could not predict a risk allele or a protective one for TE in NOS2, PTGS2, or VEGFA, although other genes should be analyzed in larger samples. The role of nitric oxide and β-catenin must be further evaluated, regarding thalidomide teratogenesis complex etiology.