First genome-wide association study on rocuronium dose requirements shows association with SLCO1A2

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Ahlström , S , Bergman , P , Jokela , R , Ottensmann , L , Ahola-Olli , A , Pirinen , M , Olkkola , K T , Kaunisto , M A & Kalso , E 2021 , ' First genome-wide association study on rocuronium dose requirements shows association with SLCO1A2 ' , British Journal of Anaesthesia , vol. 126 , no. 5 , pp. 949-957 .

Title: First genome-wide association study on rocuronium dose requirements shows association with SLCO1A2
Author: Ahlström, Sirkku; Bergman, Paula; Jokela, Ritva; Ottensmann, Linda; Ahola-Olli, Ari; Pirinen, Matti; Olkkola, Klaus T.; Kaunisto, Mari A.; Kalso, Eija
Contributor organization: Helsinki University Hospital Area
HUS Perioperative, Intensive Care and Pain Medicine
University of Helsinki
Department of Public Health
Institute for Molecular Medicine Finland
Helsinki Institute of Life Science HiLIFE
Centre of Excellence in Complex Disease Genetics
Helsinki Institute for Information Technology
Statistical and population genetics
Department of Mathematics and Statistics
Biostatistics Helsinki
Eija Kalso / Principal Investigator
Department of Pharmacology
Iiris Hovatta / Principal Investigator
Date: 2021-05
Language: eng
Number of pages: 9
Belongs to series: British Journal of Anaesthesia
ISSN: 0007-0912
Abstract: Background: Rocuronium, a common neuromuscular blocking agent, is mainly excreted unchanged in urine (10-25%) 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 (50-100 mg kg(-1) min(-1)) and remifentanil (0.05-0.25 mg kg(-1) min(-1)). Neuromuscular block was maintained with rocuronium to keep the train-of-four ratio at 0-10%. 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 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.
Subject: genome-wide association study
neuromuscular block
1184 Genetics, developmental biology, physiology
317 Pharmacy
3126 Surgery, anesthesiology, intensive care, radiology
Peer reviewed: Yes
Rights: cc_by_nc_nd
Usage restriction: openAccess
Self-archived version: publishedVersion

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