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

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 μg kg−1 min−1) and remifentanil (0.05–0.25 μg 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.