Pharmacogenetic predictors of nausea and vomiting of pregnancy severity and response to antiemetic therapy: a pilot study

Abstract

BackgroundNausea and vomiting of pregnancy (NVP) is a common condition. The objective of this study was to evaluate the association between response to antiemetics in the treatment of NVP and genetic polymorphisms in the serotonin receptor subunit genes HTR3A and HTR3B.MethodsPregnant women ≥18 years of age with NVP starting antiemetic therapy with promethazine, prochlorperazine, metoclopramide, or ondansetron at ≤ 16 weeks gestational age were eligible. The study recruited 29 women with complete data and sampling who returned for their one week follow-up and were genotyped for HTR3A and HTR3B polymorphisms. Severity of NVP was captured (using Pregnancy Unique Quantification of Emesis (PUQE) and Quality of Life (QOL) tools) upon enrollment and after one week of antiemetic therapy. These measures were correlated with pharmacogenetic variability.ResultsSubjects with genotype associated with high serotonin affinity of the 5-HT3B receptor (rs1176744, CC) required more antiemetic medications (p < 0.001) than other subjects. Those with genotypes associated with increased expression of the 5-HT3A receptor subunit (rs1062613, CT or TT) had worse final PUQE scores (p = 0.01) than other subjects while rs3782025 variants carriers had significantly better initial (p = 0.02) and final (p = 0.02) PUQE scores than other subjects.ConclusionsHTR3B and HTR3A gene variants may contribute to variability in response to antiemetic therapy for NVP.

The Human Serotonin Type 3 Receptor Gene (HTR3A-E) Allelic Variant Database

“…Carriers of the HTR3B SNP rs1176744 CC genotype required more antiemetic medications than other subjects. Carriers of the HTR3A rs1062613 genotypes CT or TT had worsened final emesis, while carriers of rs3782025 variants in HTR3B had significantly better initial and final emesis scores [Lehmann et al., ]. Distinct subgrouping of pregnant women suffering from NVP according to HTR3 genotypes of associated variants might allow an individualized antiemetic treatment in the future [Goecke et al., ].…”

“…Disease‐associated variants in HTR3 genes encode receptors with impaired structure or function, which underlines their potential as therapeutic targets and predictors of treatment response in a personalized therapeutic approach. The potential of these variants in predicting the response to treatment of CINV, PONV, NVP, and adverse effects in pharmacotherapy have been studied [Tremblay et al., ; Einarson et al., ; Kaiser et al., ; Fasching et al., ; Hammer et al., ; Rueffert et al., ; Goecke et al., ; Lehmann et al., ; Joy Lin et al., ; Kim et al., ]. Their potential in IBS, bulimia, OCD, and schizophrenia has already been demonstrated [Walstab et al., ; Lennertz et al., ].…”

Pharmacogenetics and Individualizing Drug Treatment During Pregnancy

“…For women with NVP, one study demonstrated that SNPs in 5HT3B leading to a high affinity receptor led to women needing more medication [79]. Other SNPs in the 5HT3A receptor were associated with more improvement in both NVP symptoms and quality of life [79]. This study may be an initial foray into pharmacogenetics of NVP and should be confirmed.…”

“…Variants in the 5HT3B receptor are linked to increased nausea and vomiting due to increased response to serotonin binding [78]. For women with NVP, one study demonstrated that SNPs in 5HT3B leading to a high affinity receptor led to women needing more medication [79]. Other SNPs in the 5HT3A receptor were associated with more improvement in both NVP symptoms and quality of life [79].…”

Genetics and Pharmacogenetics of Aminergic Transmitter Pathways in Functional Gastrointestinal Disorders

“…In a pilot study, Lehmann et al [115] evaluated possible associations between the efficacy of different antiemetic medications, including metoclopramide, in the control of nausea and vomiting in pregnancy with polymor phisms in HTR3A and HTR3B subunits. A group of 28 pregnant women (9 Caucasians, 17 AfroAmericans, 2 Hispanic), receiving metoclopramide, promethazine, prochlorperazine or ondansetron for nausea and vom iting, underwent assessment of symptom severity and quality of life, both at baseline and after 1 week of ther apy.…”