A Non-Synonymous Single Nucleotide Polymorphism in an <em>OPRM1</em> Splice Variant Is Associated with Fentanyl-Induced Emesis in Women Undergoing Minor Gynaecological Surgery

<div><h3>Background</h3><p>Fentanyl-induced emesis (FIE) is a distressing adverse effect in the postoperative setting. The genetic basis of FIE remains largely unknown, therefore, we examined whether it was associated with specific genetic variants of <em>OPRM1</em>, the gene encoding the main receptor target of fentanyl.</p> <h3>Methods</h3><p>In this prospective case-control study, 193 women undergoing gynaecological surgery under a standardized anaesthetic with a low emetogenic risk were enrolled. Inclusion and exclusion criteria were designed to select extreme phenotypes as well as to ensure that most major confounders for FIE were either excluded or present in all patients. To control for unforeseen intra- and postoperative confounders for FIE, only 161 patients were further analysed, out of which 10 were categorized as having FIE, defined by the presence of at least one of three symptoms: nausea, vomiting or retching that was likely to be fentanyl-related. To identify SNPs relevant to FIE in our population, DNA from 40 controls and 10 cases was sequenced at the following <em>OPRM1</em> regions: 3 kbp of the promoter, main and alternative exons as well as 2 kbp of the 3′ downstream region. The genotype of the significant SNP was further determined in the remaining 111 controls.</p> <h3>Results</h3><p>The incidence of FIE was 6.2%. Initial sequencing of 10 cases and 40 controls identified 25 SNPs. Only rs540825, a non-synonymous SNP in the splice variant, MOR1X, showed a significant association with FIE post-Bonferroni correction. This SNP was further examined in the remaining 111 controls which confirmed its significant association with FIE (p = 0.019 post-Bonferroni, OR: 5.6, 95% CI: 1.42–21.91).</p> <h3>Conclusions</h3><p>This is the first report of an association between the occurrence of FIE in Chinese women undergoing gynaecological surgery and an <em>OPRM1</em> splice variant SNP, rs540825.</p> </div

Additional file 1: of Prevalence and risk factors of intestinal parasitism among two indigenous sub-ethnic groups in Peninsular Malaysia

Multilingual abstract in the five official working languages of the United Nations. (PDF 464 kb

Additional file 2: Figure S2. of A new paradigm for Aedes spp. surveillance using gravid ovipositing sticky trap and NS1 antigen test kit

Number of dengue cases recorded during the study period (2013–2015) plotted according to the floor. (TIF 74 kb

Additional file 2: Additional tables. Table S1. of Prevalence and risk factors of intestinal parasitism among two indigenous sub-ethnic groups in Peninsular Malaysia

General characteristics of indigenous communities who participated in this study. Table S2. Predictive power of the enter and forward selection logistic regression model. (PDF 175 kb

Flowchart of study perioperative anaesthetic protocol of low emetogenicity for minor gynaecological day surgery.

<p>No prophylactic anti-emetics were given pre and intraoperatively. Total intravenous anaesthesia (TIVA) using an intravenous (IV) target controlled infusion (TCI) of propofol, was administered using a propofol infusor (Asena PK Syringe Pump, Carefusion USA). The infusor was pre-programmed with the Marsh algorithm <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0048416#pone.0048416-Marsh1" target="_blank">[18]</a>, which computed propofol dosing rates to attain a target perioperative plasma propofol concentration of 4–6 ug/ml and 3–6 ug/ml in the induction and maintenance phase of anaesthesia respectively in every patient.</p

Additional file 5: Figure S4. of A new paradigm for Aedes spp. surveillance using gravid ovipositing sticky trap and NS1 antigen test kit

Relationship between the weekly numbers of Ae. aegypti caught per trap and number of eggs per ovitrap. There was a significant correlation between the number of eggs per ovitrap (mean 12.66, range 1.52–56.81) and the number of adults caught per trap (r = 0.41, t = 4.5, df = 105, P < 0.001). (TIF 1980 kb

Additional file 3: Figure S3. of A new paradigm for Aedes spp. surveillance using gravid ovipositing sticky trap and NS1 antigen test kit

Number of dengue cases recorded during the study period (2013–2015) plotted according to the block. (TIF 66 kb

Boxplots indicating the distribution of values for 3 variables in 151 controls and 10 cases.

<p>These 3 variables could contribute to the occurrence of emesis but could not be controlled for in the study design (a) Age (b) Total propofol dose (c) Total fentanyl dose. The median is the horizontal line bisecting the shaded box of the boxplot and the median value placed adjacent to the horizontal line. There are no significant differences (p<0.05) between the median values of controls and cases for the 3 variables.</p

Flowchart outlining the patients enrolled, analysed, classified as cases or controls and sequenced for <i>OPRM1</i> SNPs.

<p>Flowchart outlining the patients enrolled, analysed, classified as cases or controls and sequenced for <i>OPRM1</i> SNPs.</p

Inclusion and exclusion criteria for study subjects.

<p>Abbreviations: KKWH: KK Womens Hospital.</p