Background: Rocuronium, a common neuromuscular blocking agent, is mainly excreted unchanged in urine (10e25%) and bile (>70%). Age, sex, liver blood flow, smoking, medical conditions, and ethnic background can affect its pharmacological actions. However, reasons for the wide variation in rocuronium requirements are mostly unknown. We hypothesised that pharmacogenetic factors might explain part of the variation. Methods: One thousand women undergoing surgery for breast cancer were studied. Anaesthesia was maintained with propofol (50e100 mg kg À1 min À1 ) and remifentanil (0.05e0.25 mg kg À1 min À1 ). Neuromuscular block was maintained with rocuronium to keep the train-of-four ratio at 0e10%. DNA was extracted from peripheral blood and genotyped with a next-generation genotyping array. The genome-wide association study (GWAS) was conducted using an additive linear regression model with PLINK software. The FINEMAP tool and data from the Genotype-Tissue Expression project v8 were utilised to study the locus further. Results: The final patient population comprised 918 individuals. Of the clinical variables tested, age, BMI, ASA physical status, and total dose of propofol correlated significantly (all P<0.001) with the rocuronium dose in a linear regression model. The GWAS highlighted one genome-wide significant locus in chromosome 12. The single-nucleotide polymorphisms (SNPs) with the most significant evidence of association were located in or near SLCO1A2. The two top SNPs, rs7967354 (P¼5.3e À11 ) and rs11045995 (P¼1.4e À10 ), and the clinical variables accounted for 41% of the variability in rocuronium dosage. Conclusions: Genetic variation in the gene SLCO1A2, encoding OATP1A2, an uptake transporter, accounted for 4% of the variability in rocuronium consumption. The underlying mechanism remains unknown.
BackgroundThe incidence of post‐operative nausea and vomiting (PONV) remains at about 30% despite all therapeutic efforts to reduce it. The clinical risk factors guiding the prophylactic treatment are well established, but genetic factors associated with PONV remain poorly known. The aim of this study was to explore clinical and genetic factors impacting PONV by performing a genome‐wide association study (GWAS) together with relevant clinical factors as covariates, and systematically attempt to replicate previously reported PONV associations. Relevant clinical factors are explored with logistic regression model.MethodsThis was an observational case control study in Helsinki University Hospital between 1 August 2006 and 31 December 2010. One thousand consenting women with elevated risk for PONV, undergoing breast cancer surgery with standardised propofol anaesthesia and antiemetics. After exclusions for clinical reasons and failed genotyping, 815 patients were included with 187 PONV cases and 628 controls. Emergence of PONV up to 7th post‐operative day was recorded. PONV at 2–24 h after surgery was selected to be the primary outcome. The GWAS explored associations between PONV and 653 034 genetic variants. Replication attempts included 31 variants in 16 genes.ResultsThe overall incidence of PONV up to 7th post‐operative day was 35%, where 3% had PONV at 0–2 h and 23% at 2–24 h after surgery. Age, American Society of Anaesthesiologists status, the amount of oxycodone used in the post‐anaesthesia care unit, smoking status, previous PONV, and history of motion sickness were statistically significant predictive factors in the logistic model. The receiver operating characteristic‐area under the curve of 0.75 (95% CI 0.71–0.79) was calculated for the model. The GWAS identified six variants with suggestive association to PONV (p < 1 × 10−5). Of the previously reported variants, association with the DRD2 variant rs18004972 (TaqIA) was replicated (p = .028).ConclusionsOur GWAS approach did not identify any high‐impact PONV susceptibility variants. The results provide some support for a role of dopamine D2 receptors in PONV.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.