Genetic Susceptibility to Drug Teratogenicity: A Systematic Literature Review.

Autor:	Gomes JDA; Programa de Pós-Graduação em Genética e Biologia Molecular (PPGBM), Departamento de Genética, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.; Sistema Nacional de Informação sobre Agentes Teratogênicos (SIAT), Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil.; Laboratório de Medicina Genômica, Centro de Pesquisa Experimental, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil.; Instituto Nacional de Genética Médica Populacional (INAGEMP), Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil., Olstad EW; Pharmacoepidemiology and Drug Safety Research Group, Department of Pharmacy, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway.; PharmaTox Strategic Research Initiative, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway., Kowalski TW; Programa de Pós-Graduação em Genética e Biologia Molecular (PPGBM), Departamento de Genética, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.; Laboratório de Medicina Genômica, Centro de Pesquisa Experimental, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil.; Instituto Nacional de Genética Médica Populacional (INAGEMP), Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil.; Complexo de Ensino Superior de Cachoeirinha (CESUCA), Cachoeirinha, Brazil., Gervin K; Pharmacoepidemiology and Drug Safety Research Group, Department of Pharmacy, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway.; PharmaTox Strategic Research Initiative, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway.; Division of Clinical Neuroscience, Department of Research and Innovation, Oslo University Hospital, Oslo, Norway., Vianna FSL; Programa de Pós-Graduação em Genética e Biologia Molecular (PPGBM), Departamento de Genética, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.; Sistema Nacional de Informação sobre Agentes Teratogênicos (SIAT), Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil.; Laboratório de Medicina Genômica, Centro de Pesquisa Experimental, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil.; Instituto Nacional de Genética Médica Populacional (INAGEMP), Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil., Schüler-Faccini L; Programa de Pós-Graduação em Genética e Biologia Molecular (PPGBM), Departamento de Genética, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.; Sistema Nacional de Informação sobre Agentes Teratogênicos (SIAT), Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil.; Instituto Nacional de Genética Médica Populacional (INAGEMP), Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil., Nordeng HME; Pharmacoepidemiology and Drug Safety Research Group, Department of Pharmacy, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway.; PharmaTox Strategic Research Initiative, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway.; Department of Child Health and Development, Norwegian Institute of Public Health, Oslo, Norway.
Jazyk:	angličtina
Zdroj:	Frontiers in genetics [Front Genet] 2021 Apr 27; Vol. 12, pp. 645555. Date of Electronic Publication: 2021 Apr 27 (Print Publication: 2021).
DOI:	10.3389/fgene.2021.645555
Abstrakt:	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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Gomes, Olstad, Kowalski, Gervin, Vianna, Schüler-Faccini and Nordeng.)
Databáze:	MEDLINE
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