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

BACKGROUND Nausea 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. METHODS Pregnant 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. RESULTS Subjects 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. CONCLUSIONS HTR3B and HTR3A gene variants may contribute to variability in response to antiemetic therapy for NVP.