Pharmacogenomics of Preeclampsia therapies: Current evidence and future challenges for clinical implementation.

Abstract

Preeclampsia is a pregnancy-specific disorder, and it is a leading cause of maternal and perinatal morbidity and mortality. The application of pharmacogenetics to antihypertensive agents and dose selection in women with preeclampsia is still in its infancy. No current prescribing guidelines from the clinical pharmacogenetics implementation consortium (CPIC) exist for preeclampsia. Although more studies on pharmacogenomics are underway, there is some evidence for the pharmacogenomics of preeclampsia therapies, considering both the pharmacokinetic (PK) and pharmacodynamic (PD) properties of drugs used in preeclampsia. It has been revealed that the CYP2D6*10 variant is significantly higher in women with preeclampsia who are non-responsive to labetalol compared to those who are in the responsive group. Various genetic variants of PD targets, i.e., NOS3, MMP9, MMP2, TIMP1, TIMP3, VEGF, and NAMPT, have been investigated to assess the responsiveness of antihypertensive therapies in preeclampsia management, and they indicated that certain genetic variants of MMP9, TIMP1, and NAMPT are more frequently observed in those who are non-responsive to anti-hypertensive therapies compared to those who are responsive. Further, gene-gene interactions have revealed that NAMPT, TIMP1, and MMP2 genotypes are associated with an increased risk of preeclampsia, and they are more frequently observed in the non-responsive subgroup of women with preeclampsia. The current evidence is not rigorous enough for clinical implementation; however, an institutional or regional-based retrospective analysis of audited data may help close the knowledge gap during the transitional period from a traditional approach (a "one-size-fits-all" strategy) to the pharmacogenomics of preeclampsia therapies.

• Authors: Piya Chaemsaithong, Mohitosh Biswas, Waranyu Lertrut, Puntabut Warintaksa, Tuangsit Wataganara, Liona Cy Poon, Chonlaphat Sukasem
• Journal: Best practice & research. Clinical obstetrics & gynaecology (Best Pract Res Clin Obstet Gynaecol) Vol. 92 Pg. 102437 (Feb 2024) ISSN: 1532-1932 [Electronic] Netherlands
• PMID: 38103508 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.

Chemical References

• Matrix Metalloproteinase 2
• Matrix Metalloproteinase 9
• Antihypertensive Agents
• Labetalol

Topics

• Pregnancy
• Female
• Humans
• Pre-Eclampsia (drug therapy, genetics)
• Pharmacogenetics
• Matrix Metalloproteinase 2
• Matrix Metalloproteinase 9 (therapeutic use)
• Retrospective Studies
• Antihypertensive Agents (therapeutic use)
• Labetalol (adverse effects)