ヤマグチ　シゲキ   YAMAGUCHI SHIGEKI   山口　茂樹    所属   医学部 医学科（東京女子医科大学病院）    職種   教授・基幹分野長
論文種別	原著
言語種別	英語
査読の有無	査読なし
表題	Genome-Wide Association Study Identifies Genetic Polymorphisms Associated with Estimated Minimum Effective Concentration of Fentanyl in Patients Undergoing Laparoscopic-Assisted Colectomy
掲載誌名	正式名：International journal of molecular sciences 略　 称：Int J Mol Sci ISSNコード：14220067/14220067
掲載区分	国外
巻・号・頁	24(9),pp.8421
著者・共著者	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
発行年月	2023/05
概要	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