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Research ArticleFree Access

Prenatal exposure to serotonin reuptake inhibitors and congenital heart anomalies: an exploratory pharmacogenetics study

    Aizati N A Daud

    *Author for correspondence:

    E-mail Address: aizati.daud@gmail.com

    Unit of PharmacoTherapy, -Epidemiology & -Economics, Department of Pharmacy, University of Groningen, Groningen Research Institute of Pharmacy, Groningen, The Netherlands

    School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia

    ,
    Jorieke E H Bergman

    Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

    ,
    Wilhelmina S Kerstjens-Frederikse

    Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

    ,
    Pieter van der Vlies

    Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

    ,
    Eelko Hak

    Unit of PharmacoTherapy, -Epidemiology & -Economics, Department of Pharmacy, University of Groningen, Groningen Research Institute of Pharmacy, Groningen, The Netherlands

    ,
    Rolf M F Berger

    Department of Pediatric Cardiology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands

    ,
    Henk Groen

    Department of Epidemiology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands

    &
    Bob Wilffert

    Unit of PharmacoTherapy, -Epidemiology & -Economics, Department of Pharmacy, University of Groningen, Groningen Research Institute of Pharmacy, Groningen, The Netherlands

    Department of Clinical Pharmacy & Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

    Published Online:https://doi.org/10.2217/pgs-2017-0036

    Aim: To explore the role of pharmacogenetics in determining the risk of congenital heart anomalies (CHA) with prenatal use of serotonin reuptake inhibitors. Methods: We included 33 case-mother dyads and 2 mother-only (child deceased) cases of CHA in a case-only study. Ten genes important in determining fetal exposure to serotonin reuptake inhibitors were examined: CYP1A2, CYP2C9, CYP2C19, CYP2D6, ABCB1, SLC6A4, HTR1A, HTR1B, HTR2A and HTR3B. Results: Among the exposed cases, polymorphisms that tended to be associated with an increased risk of CHA were SLC6A4 5-HTTLPR and 5-HTTVNTR, HTR1A rs1364043, HTR1B rs6296 and rs6298 and HTR3B rs1176744, but none reached statistical significance due to our limited sample sizes. Conclusion: We identified several polymorphisms that might potentially affect the risk of CHA among exposed fetuses, which warrants further investigation.

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

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