JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
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Genetic susceptibility to thalidomide embryopathy in humans: Study of candidate development genes.

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.

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