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Genetic susceptibility to thalidomide embryopathy in humans: Study of candidate development genes
Author(s) -
Gomes Julia do Amaral,
Kowalski Thayne Woycinck,
Fraga Lucas Rosa,
TovoRodrigues Luciana,
Sanseverino Maria Teresa Vieira,
SchulerFaccini Lavínia,
Vianna Fernanda Sales Luiz
Publication year - 2018
Publication title -
birth defects research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.845
H-Index - 17
ISSN - 2472-1727
DOI - 10.1002/bdr2.1163
Subject(s) - thalidomide , gene , genetics , biology , allele , ubiquitin ligase , genotype , candidate gene , bioinformatics , ubiquitin , immunology , multiple myeloma
Thalidomide is a drug used worldwide for several indications, but the molecular mechanisms of its teratogenic property are not fully understood. Studies in animal models suggest the oxidative stress, the inhibition of angiogenesis, and the binding to E3‐ubiquitin ligase complex as mechanisms by which thalidomide can change the expression of genes important to embryonic development. In this study, seven polymorphisms in genes related to development ( FGF8 , FGF10 , BMP4 , SHH , TP53, TP63 , and TP73) were analyzed in people with thalidomide embryopathy (TE) and compared to people without malformations. The sample consisted of 36 people with TE and 135 unrelated and nonsyndromic people who had their DNA genotyped by PCR real‐time. Although no allelic or genotypic differences were observed between the groups, we hypothesized that other regions in these genes and related genes may play an important role in thalidomide teratogenesis, which is known to have a genetic contribution. Identifying such molecular mechanisms is essential for the development of a molecule that will be analogue to thalidomide but safe enough to avoid the emergence of new cases of TE.