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

作者：Kowalski Thayne Woycinck; Fraga Lucas Rosa; Tovo Rodrigues Luciana; Vieira Sanseverino Maria Teresa; Hutz Mara Helena; Schuler Faccini Lavinia; Luiz Vianna Fernanda Sales

来源：Reproductive Toxicology, 2017, 70: 133-140.

DOI：10.1016/j.reprotox.2017.01.012

• Nitric oxide
• In-silico analyses
• Embryopathy
• Human embryonal cells

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 beta-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 beta-catenin must be further evaluated, regarding thalidomide teratogenesis complex etiology.

• 出版日期2017-6