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

Author:

Daud Aizati N A12,Bergman Jorieke E H3,Kerstjens-Frederikse Wilhelmina S3,van der Vlies Pieter3,Hak Eelko1,Berger Rolf M F4,Groen Henk5,Wilffert Bob16

Affiliation:

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

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

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

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

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

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

Abstract

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.

Publisher

Future Medicine Ltd

Subject

Pharmacology,Genetics,Molecular Medicine

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