Calcium channel blockers as drug repurposing candidates for gestational diabetes: Mining large scale genomic and electronic health records data to repurpose medications.
Pharmacol Res
; 130: 44-51, 2018 04.
Article
em En
| MEDLINE
| ID: mdl-29448118
ABSTRACT
New therapeutic approaches are needed for gestational diabetes mellitus (GDM), but must show safety and efficacy in a historically understudied population. We studied associations between electronic medical record (EMR) phenotypes and genetic variants to uncover drugs currently considered safe in pregnancy that could treat or prevent GDM. We identified 129 systemically active drugs considered safe in pregnancy targeting the proteins produced from 196 genes. We tested for associations between GDM and/or type 2 diabetes (DM2) and 306 SNPs in 130 genes represented on the Illumina Infinium Human Exome Bead Chip (DM2 was included due to shared pathophysiological features with GDM). In parallel, we tested the association between drugs and glucose tolerance during pregnancy as measured by the glucose recorded during a routine 50-g glucose tolerance test (GTT). We found an association between GDM/DM2 and the genes targeted by 11 drug classes. In the EMR analysis, 6 drug classes were associated with changes in GTT. Two classes were identified in both analyses. L-type calcium channel blocking antihypertensives (CCBs), were associated with a 3.18â¯mg/dL (95% CI -6.18 to -0.18) decrease in glucose during GTT, and serotonin receptor type 3 (5HT-3) antagonist antinausea medications were associated with a 3.54â¯mg/dL (95% CI 1.86-5.23) increase in glucose during GTT. CCBs were identified as a class of drugs considered safe in pregnancy could have efficacy in treating or preventing GDM. 5HT-3 antagonists may be associated with worse glucose tolerance.
Palavras-chave
Anxiety; Calcium channel blockers; Drug repurposing; Drug safety; Electronic health records; Gene set enrichment analysis; Gestational diabetes; Glucose tolerance; Hyperemesis; Hypertension; International classification of disease; Major depressive disorder; Placenta; Pregnancy complications; Serotonin
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Bloqueadores dos Canais de Cálcio
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Diabetes Gestacional
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Reposicionamento de Medicamentos
Tipo de estudo:
Prognostic_studies
Limite:
Adolescent
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Adult
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Female
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Humans
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Middle aged
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Pregnancy
Idioma:
En
Revista:
Pharmacol Res
Assunto da revista:
FARMACOLOGIA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Estados Unidos