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

Reprod Toxicol

INAGEMP-Instituto Nacional de Genética Médica Populacional, Porto Alegre, Brazil; Post-Graduate Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Teratogen Information Service, Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Brazil; Service of Experimental Research, Genomics Medicine Laboratory, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil. Electronic address:

Published: June 2017

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.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.reprotox.2017.01.012DOI Listing

Publication Analysis

Top Keywords

angiogenesis-related genes
8
thalidomide teratogenesis
8
vitro studies
8
angiogenesis-related molecules
8
nos2 ptgs2
8
ptgs2 vegfa
8
nitric oxide
8
oxide β-catenin
8
thalidomide
5
angiogenesis-related
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!