YAMAGUCHI SHIGEKI
   Department   School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine
   Position   Professor and Division head
Article types Original article
Language English
Peer review Non peer reviewed
Title Genome-Wide Association Study Identifies Genetic Polymorphisms Associated with Estimated Minimum Effective Concentration of Fentanyl in Patients Undergoing Laparoscopic-Assisted Colectomy
Journal Formal name：International journal of molecular sciences
Abbreviation：Int J Mol Sci
ISSN code：14220067/14220067
Domestic / ForeginForegin
Volume, Issue, Page 24(9),pp.8421
Author and coauthor NISHIZAWA Daisuke, MIEDA Tsutomu, TSUJITA Miki, NAKAGAWA Hideyuki, YAMAGUCHI Shigeki, KASAI Shinya, HASEGAWA Junko, NAKAYAMA Kyoko, EBATA Yuko, KITAMURA Akira, SHIMIZU Hirotomo, TAKASHIMA Tadayuki, HAYASHIDA Masakazu, IKEDA Kazutaka
Publication date 2023/05
Summary Sensitivity to opioids varies widely among individuals. To identify potential candidate single-nucleotide polymorphisms (SNPs) that may significantly contribute to individual differences in the minimum effective concentration (MEC) of an opioid, fentanyl, we conducted a three-stage genome-wide association study (GWAS) using whole-genome genotyping arrays in 350 patients who underwent laparoscopic-assisted colectomy. To estimate the MEC of fentanyl, plasma and effect-site concentrations of fentanyl over the 24 h postoperative period were estimated with a pharmacokinetic simulation model based on initial bolus doses and subsequent patient-controlled analgesia doses of fentanyl. Plasma and effect-site MECs of fentanyl were indicated by fentanyl concentrations, estimated immediately before each patient-controlled analgesia dose. The GWAS revealed that an intergenic SNP, rs966775, that mapped to 5p13 had significant associations with the plasma MEC averaged over the 6 h postoperative period and the effect-site MEC averaged over the 12 h postoperative period. The minor G allele of rs966775 was associated with increases in these MECs of fentanyl. The nearest protein-coding gene around this SNP was DRD1, encoding the dopamine D1 receptor. In the gene-based analysis, the association was significant for the SERP2 gene in the dominant model. Our findings provide valuable information for personalized pain treatment after laparoscopic-assisted colectomy.
DOI 10.3390/ijms24098421
PMID 37176129