The Association of CYP2D6 Genotype and Postoperative Nausea and Vomiting in Orthopedic Trauma Patients

Abstract

<jats:p>The CYP2D6 gene encodes for an enzyme that is involved in the metabolism of more than 25% of all medications, including many opioids and antiemetics. It may contribute to the risk of postoperative nausea and vomiting (PONV), a common surgical complication. However, little research has been conducted in this area. The purpose of this study was to explore the association of CYP2D6 genotypes with PONV in adult surgical trauma patients. Data from 112 patients (28% female) with single extremity fractures, aged 18–70 years, were analyzed. PONV was defined as present if patients reported nausea, were observed vomiting, or received medication for PONV. Saliva samples collected for DNA extraction and Taqman<jats:sup>®</jats:sup>allele discrimination and quantitative real time polymerase chain reaction (qRT-PCR) were used to collect genotype data that were then used to assign CYP2D6 phenotype classification. The incidence of PONV was 38% in the postanesthesia care unit and increased to 50% when assessed at 48 hr. CYP2D6 classification results were 7 (6%) poor metabolizers, 34 (30%) intermediate metabolizers, and 71 (63%) extensive metabolizers. No ultrarapid metabolizers were identified. Patients who were classified as poor metabolizers had less PONV and higher pain scores. Gender and history of PONV, but not smoking, were also significant risk factors. Findings suggest variability in CYP2D6 impacts susceptibility to PONV.</jats:p>

Pharmacogenetics of Chemotherapy-Induced Nausea and Vomiting

“…For example, homozygous carriers of CYP2D6*3A (rs35742686) or CYP2D6*4 (rs3892097) variants are classified as poor metabolizers. These mutant alleles could theoretically result in fewer symptoms of CINV because of decreased metabolism of 5-HT 3 receptor antagonists [48]. However, no significant associations of SNPs of the CYP2D6 gene with CINV have been reported so far.…”

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

“…Because the first choice of antiemetic medications are serotonin receptor antagonists (Gan et al, 2014), we first focused on the genes of the serotonin pathway and the CYP450 family (hepatic enzymes responsible for the metabolism of these medications). We found that individuals characterized as CYP2D6 poor metabolizers experience increased PONV (Wesmiller et al, 2013). We also found that variability in the promoter region of the serotonin transport gene was associated with increased nausea and vomiting in women with breast cancer after surgery yet prior to initiation of adjuvant chemotherapy (Wesmiller et al, 2014).…”

“…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). Type and duration of anesthesia, and medications used during the surgical procedures are also known be associated with PONV (Gan et al, 2014; Janicki et al, 2011).…”

Postoperative nausea and vomiting

“…The most common types of genetic study associated with PONV are those of the single nucleotide polymorphisms associated with neural signaling and transmitter receptors in the PONV system. Genes regarded as related to PONV or OINV include 5-HT 3 (subunit A and B) receptor [7], muscarinic type 3 receptor, dopamine type 2 receptors [8], catechol-o-methyl-transferase [9], alpha 2 adrenoceptors [10], adenosine triphosphate-binding cassette subfamily B member 1 [11], cytochrome P450 superfamily enzyme [12], and UDP-glucuronosyltransferase.…”