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

Pharmacogenomics. 2017 Jul;18(10):987-1001. doi: 10.2217/pgs-2017-0036. Epub 2017 Jun 22.

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.

Keywords: gene–environment interaction; heart defects; pharmacogenetics; serotonin reuptake inhibitors; teratogenicity.

MeSH terms

  • Female
  • Fetal Development / drug effects
  • Genotype
  • Heart Defects, Congenital / chemically induced*
  • Heart Defects, Congenital / genetics
  • Humans
  • Infant, Newborn
  • Male
  • Maternal Exposure / adverse effects*
  • Pharmacogenomic Variants*
  • Polymorphism, Single Nucleotide*
  • Pregnancy
  • Prenatal Exposure Delayed Effects / chemically induced*
  • Prenatal Exposure Delayed Effects / genetics
  • Selective Serotonin Reuptake Inhibitors / adverse effects*
  • Selective Serotonin Reuptake Inhibitors / pharmacokinetics
  • Selective Serotonin Reuptake Inhibitors / therapeutic use

Substances

  • Serotonin Uptake Inhibitors