Genetic susceptibility to drug teratogenicity: a systematic literature review
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFRGS |
Texto Completo: | http://hdl.handle.net/10183/255548 |
Resumo: | Since the 1960s, drugs have been known to cause teratogenic effects in humans. Such teratogenicity has been postulated to be influenced by genetics. The aim of this review was to provide an overview of the current knowledge on genetic susceptibility to drug teratogenicity in humans and reflect on future directions within the field of genetic teratology. We focused on 12 drugs and drug classes with evidence of teratogenic action, as well as 29 drugs and drug classes with conflicting evidence of fetal safety in humans. An extensive literature search was performed in the PubMed and EMBASE databases using terms related to the drugs of interest, congenital anomalies and fetal development abnormalities, and genetic variation and susceptibility. A total of 29 studies were included in the final data extraction. The eligible studies were published between 1999 and 2020 in 10 different countries, and comprised 28 candidate gene and 1 whole-exome sequencing studies. The sample sizes ranged from 20 to 9,774 individuals. Several drugs were investigated, including antidepressants (nine studies), thalidomide (seven studies), antiepileptic drugs (five studies), glucocorticoids (four studies), acetaminophen (two studies), and sex hormones (estrogens, one study; 17-alpha hydroxyprogesterone caproate, one study). The main neonatal phenotypic outcomes included perinatal complications, cardiovascular congenital anomalies, and neurodevelopmental outcomes. The review demonstrated that studies on genetic teratology are generally small, heterogeneous, and exhibit inconsistent results. The most convincing findings were genetic variants in SLC6A4, MTHFR, and NR3C1, which were associated with drug teratogenicity by antidepressants, antiepileptics, and glucocorticoids, respectively. Notably, this review demonstrated the large knowledge gap regarding genetic susceptibility to drug teratogenicity, emphasizing the need for further efforts in the field. Future studies may be improved by increasing the sample size and applying genome-wide approaches to promote the interpretation of results. Such studies could support the clinical implementation of genetic screening to provide safer drug use in pregnant women in need of drugs. |
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Gomes, Julia do AmaralOlstad, Emilie WillochKowalski, Thayne WoycinckGervin, KristinaVianna, Fernanda Sales LuizFaccini, Lavinia SchulerNordeng, Hedvig Marie Egeland2023-03-10T03:26:54Z20211664-8021http://hdl.handle.net/10183/255548001153896Since the 1960s, drugs have been known to cause teratogenic effects in humans. Such teratogenicity has been postulated to be influenced by genetics. The aim of this review was to provide an overview of the current knowledge on genetic susceptibility to drug teratogenicity in humans and reflect on future directions within the field of genetic teratology. We focused on 12 drugs and drug classes with evidence of teratogenic action, as well as 29 drugs and drug classes with conflicting evidence of fetal safety in humans. An extensive literature search was performed in the PubMed and EMBASE databases using terms related to the drugs of interest, congenital anomalies and fetal development abnormalities, and genetic variation and susceptibility. A total of 29 studies were included in the final data extraction. The eligible studies were published between 1999 and 2020 in 10 different countries, and comprised 28 candidate gene and 1 whole-exome sequencing studies. The sample sizes ranged from 20 to 9,774 individuals. Several drugs were investigated, including antidepressants (nine studies), thalidomide (seven studies), antiepileptic drugs (five studies), glucocorticoids (four studies), acetaminophen (two studies), and sex hormones (estrogens, one study; 17-alpha hydroxyprogesterone caproate, one study). The main neonatal phenotypic outcomes included perinatal complications, cardiovascular congenital anomalies, and neurodevelopmental outcomes. The review demonstrated that studies on genetic teratology are generally small, heterogeneous, and exhibit inconsistent results. The most convincing findings were genetic variants in SLC6A4, MTHFR, and NR3C1, which were associated with drug teratogenicity by antidepressants, antiepileptics, and glucocorticoids, respectively. Notably, this review demonstrated the large knowledge gap regarding genetic susceptibility to drug teratogenicity, emphasizing the need for further efforts in the field. Future studies may be improved by increasing the sample size and applying genome-wide approaches to promote the interpretation of results. Such studies could support the clinical implementation of genetic screening to provide safer drug use in pregnant women in need of drugs.application/pdfengFrontiers in Genetics. Lausanne. Vol. 12, (Abr. 2021), e645555, 20 p.TeratógenosTalidomidaAntidepressivosAnticonvulsivantesPredisposição genética para doençaGravidezExposição maternaPrenatal exposuresTeratogensPregnancyCongenital anomaliesThalidomideAntidepressantAnticonvulsantsGenetic predisposition to diseaseGenetic susceptibility to drug teratogenicity: a systematic literature reviewEstrangeiroinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRGSinstname:Universidade Federal do Rio Grande do Sul (UFRGS)instacron:UFRGSTEXT001153896.pdf.txt001153896.pdf.txtExtracted Texttext/plain95337http://www.lume.ufrgs.br/bitstream/10183/255548/2/001153896.pdf.txt6883c8ebb521b715d087b50a6bfefdcbMD52ORIGINAL001153896.pdfTexto completo (inglês)application/pdf664134http://www.lume.ufrgs.br/bitstream/10183/255548/1/001153896.pdfae2dc918fbce367166afb352c1b5ef2cMD5110183/2555482023-03-11 03:30:48.701484oai:www.lume.ufrgs.br:10183/255548Repositório de PublicaçõesPUBhttps://lume.ufrgs.br/oai/requestopendoar:2023-03-11T06:30:48Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS)false |
dc.title.pt_BR.fl_str_mv |
Genetic susceptibility to drug teratogenicity: a systematic literature review |
title |
Genetic susceptibility to drug teratogenicity: a systematic literature review |
spellingShingle |
Genetic susceptibility to drug teratogenicity: a systematic literature review Gomes, Julia do Amaral Teratógenos Talidomida Antidepressivos Anticonvulsivantes Predisposição genética para doença Gravidez Exposição materna Prenatal exposures Teratogens Pregnancy Congenital anomalies Thalidomide Antidepressant Anticonvulsants Genetic predisposition to disease |
title_short |
Genetic susceptibility to drug teratogenicity: a systematic literature review |
title_full |
Genetic susceptibility to drug teratogenicity: a systematic literature review |
title_fullStr |
Genetic susceptibility to drug teratogenicity: a systematic literature review |
title_full_unstemmed |
Genetic susceptibility to drug teratogenicity: a systematic literature review |
title_sort |
Genetic susceptibility to drug teratogenicity: a systematic literature review |
author |
Gomes, Julia do Amaral |
author_facet |
Gomes, Julia do Amaral Olstad, Emilie Willoch Kowalski, Thayne Woycinck Gervin, Kristina Vianna, Fernanda Sales Luiz Faccini, Lavinia Schuler Nordeng, Hedvig Marie Egeland |
author_role |
author |
author2 |
Olstad, Emilie Willoch Kowalski, Thayne Woycinck Gervin, Kristina Vianna, Fernanda Sales Luiz Faccini, Lavinia Schuler Nordeng, Hedvig Marie Egeland |
author2_role |
author author author author author author |
dc.contributor.author.fl_str_mv |
Gomes, Julia do Amaral Olstad, Emilie Willoch Kowalski, Thayne Woycinck Gervin, Kristina Vianna, Fernanda Sales Luiz Faccini, Lavinia Schuler Nordeng, Hedvig Marie Egeland |
dc.subject.por.fl_str_mv |
Teratógenos Talidomida Antidepressivos Anticonvulsivantes Predisposição genética para doença Gravidez Exposição materna |
topic |
Teratógenos Talidomida Antidepressivos Anticonvulsivantes Predisposição genética para doença Gravidez Exposição materna Prenatal exposures Teratogens Pregnancy Congenital anomalies Thalidomide Antidepressant Anticonvulsants Genetic predisposition to disease |
dc.subject.eng.fl_str_mv |
Prenatal exposures Teratogens Pregnancy Congenital anomalies Thalidomide Antidepressant Anticonvulsants Genetic predisposition to disease |
description |
Since the 1960s, drugs have been known to cause teratogenic effects in humans. Such teratogenicity has been postulated to be influenced by genetics. The aim of this review was to provide an overview of the current knowledge on genetic susceptibility to drug teratogenicity in humans and reflect on future directions within the field of genetic teratology. We focused on 12 drugs and drug classes with evidence of teratogenic action, as well as 29 drugs and drug classes with conflicting evidence of fetal safety in humans. An extensive literature search was performed in the PubMed and EMBASE databases using terms related to the drugs of interest, congenital anomalies and fetal development abnormalities, and genetic variation and susceptibility. A total of 29 studies were included in the final data extraction. The eligible studies were published between 1999 and 2020 in 10 different countries, and comprised 28 candidate gene and 1 whole-exome sequencing studies. The sample sizes ranged from 20 to 9,774 individuals. Several drugs were investigated, including antidepressants (nine studies), thalidomide (seven studies), antiepileptic drugs (five studies), glucocorticoids (four studies), acetaminophen (two studies), and sex hormones (estrogens, one study; 17-alpha hydroxyprogesterone caproate, one study). The main neonatal phenotypic outcomes included perinatal complications, cardiovascular congenital anomalies, and neurodevelopmental outcomes. The review demonstrated that studies on genetic teratology are generally small, heterogeneous, and exhibit inconsistent results. The most convincing findings were genetic variants in SLC6A4, MTHFR, and NR3C1, which were associated with drug teratogenicity by antidepressants, antiepileptics, and glucocorticoids, respectively. Notably, this review demonstrated the large knowledge gap regarding genetic susceptibility to drug teratogenicity, emphasizing the need for further efforts in the field. Future studies may be improved by increasing the sample size and applying genome-wide approaches to promote the interpretation of results. Such studies could support the clinical implementation of genetic screening to provide safer drug use in pregnant women in need of drugs. |
publishDate |
2021 |
dc.date.issued.fl_str_mv |
2021 |
dc.date.accessioned.fl_str_mv |
2023-03-10T03:26:54Z |
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Estrangeiro info:eu-repo/semantics/article |
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http://hdl.handle.net/10183/255548 |
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Frontiers in Genetics. Lausanne. Vol. 12, (Abr. 2021), e645555, 20 p. |
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