Genetic factors associated with pharmacotherapy and background sensitivity to postoperative and chemotherapy-induced nausea and vomiting

Abstract

Postoperative nausea and vomiting (PONV) continues to be a most common complication of surgery and anesthesia. It has been suggested that the inherited factors may play a significant role in the background sensitivity to both PONV and also chemotherapy-induced nausea and vomiting (CINV), including resistance to antiemetic prophylaxis and/or therapy. This notion could be best exemplified by occurrence of PONV in several generations of families and concordance of PONV in monozygotic twins. The most frequently addressed issue in the research on genomic background of PONV/CINV relates to the inherited resistance to the antiemetic treatment (pharmacogenomics), and in lesser degree to their genomic background. The most common group of antiemetics consists of 5HT3 receptor antagonists, and this group was an initial target of pharmacogenomic research. Most research approaches have been based on the investigation of polymorphic variations in the target for the antiemetic 5HT3 receptor antagonists, i.e., serotonin receptor subunits A and B (HTR3A and HTR3B). The other area of pharmacogenomic investigations includes metabolic pathways of 5HT3 antagonists, in particular polymorphic variants of the CYP450 2D6 isoform (CYP2D6) because most of them are metabolized in various degrees by the CYP2D6 system. The results of targeted genomic association studies indicate that other genes are also associated with PONV and CINV, including OPRM1, and ABCB1. In addition, genes such as DRD2 and CHRM3 genes have recently been associated with PONV. The new genome-wide association studies seem also to indicate that the background genomic sensitivity to PONV and CINV might be multifactorial and include several genomic pathways.

Pharmacogenetics of Chemotherapy-Induced Nausea and Vomiting

“…In this respect, there are increasing lines of evidence indicating that there is a hereditary character to sensitivity to motion sickness [26], and also to postoperative nausea and vomiting (PONV) [24]. It is therefore likely that a genetic background similar to that responsible for increased sensitivity to motion sickness and PONV might be involved in increased sensitivity to CINV, although experimental data confirming this hypothesis are not yet available.…”

“…Individual differences in the sensitivity to, and metabolism of, antiemetic drugs were reported previously [23]. Recent reports have shown that genetic polymorphisms of several known genes, in several metabolic pathways, were associated with CINV [2,24]. Some of them are SNPs of the HTR3 and TACR1 genes, which encode 5-HT 3 and NK 1 receptors, respectively.…”

Exploring the multifactorial nature of postoperative nausea and vomiting in women following surgery for breast cancer

“…(Miaskowski, 2009; Jolley, 2001). PONV is one of the strongest predictors of prolonged hospital stay and unanticipated admission for outpatient surgery patients accounting for millions of dollars of health care costs annually (Gan et al, 2014; Janicki and Sugino, 2014; Marla and Stallard, 2009). The use of opioids for postoperative pain has long been recognized as a primary predictor of PONV, and other known predictors include female gender, a negative smoking history and previous experience of PONV or motion sickness (Apfel et al, 2008; Meng and Quinlan, 2006; Murphy et al, 2006; Wesmiller et al, 2013; White et al, 2008).…”

TACR1 gene polymorphism and sex differences in postoperative nausea and vomiting

“…Recent studies have suggested that single nucleotide polymorphisms (SNPs) in several genes are involved in PONV . The DRD2 gene which encodes dopamine receptors, and the 5HT3A and 5HT3B genes which encode serotonin receptors, have polymorphisms that have been associated with PONV .…”

“…The DRD2 gene which encodes dopamine receptors, and the 5HT3A and 5HT3B genes which encode serotonin receptors, have polymorphisms that have been associated with PONV . With respect to metabolic enzymes, SNPs in the CYP2D6 gene have been shown to contribute to attenuation of the effect of antiemetic agents . A genome‐wide association study has also found that SNPs in the CHRM3 gene, which encodes muscarinic acetylcholine receptors, are associated with PONV .…”