title: Genome-wide association study identifies candidate loci associated with postoperative fentanyl requirements after laparoscopic-assisted colectomy.
abstract: OBJECTIVE
  Opioids are widely used as effective analgesics, but opioid sensitivity is well known to vary widely among individuals and the underlying genetic factors are not fully understood, thus hampering efficient pain treatment. We explored the genetic factors that contribute to individual differences in opioid sensitivity by performing a genome-wide association study.
  
  
  METHODS
  We conducted a multistage genome-wide association study in subjects who underwent laparoscopic-assisted colectomy (LAC).
  
  
  RESULTS
  A nonsynonymous SNP in the LAMB3 gene region, rs2076222, was strongly associated with postoperative opioid requirements. The C allele of this best-candidate SNP was associated with lower opioid sensitivity and/or higher pain sensitivity in the patient subjects.
  
  
  CONCLUSIONS
  Our findings provide valuable information for personalized pain treatment after LAC, in which the C allele of the rs2076222 SNP is associated with lower opioid sensitivity and requires more opioid analgesic after LAC.
authors.affiliation: Department of Anesthesiology, Saitama Medical University International Medical Center, 1397-1, Yamane, Hidaka, Saitama 350-1298, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Mieda
authors.affiliation: Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, 2-1-6, Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nishizawa
authors.affiliation: Department of Anesthesiology, Saitama Medical University International Medical Center, 1397-1, Yamane, Hidaka, Saitama 350-1298, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Nakagawa
authors.affiliation: Department of Anesthesiology, Saitama Medical University International Medical Center, 1397-1, Yamane, Hidaka, Saitama 350-1298, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Tsujita
authors.affiliation: Department of Anesthesiology, Saitama Medical University International Medical Center, 1397-1, Yamane, Hidaka, Saitama 350-1298, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Imanishi
authors.affiliation: Department of Anesthesiology, Saitama Medical University International Medical Center, 1397-1, Yamane, Hidaka, Saitama 350-1298, Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Terao
authors.affiliation: Department of Anesthesiology, Saitama Medical University International Medical Center, 1397-1, Yamane, Hidaka, Saitama 350-1298, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Yoshikawa
authors.affiliation: Department of Anesthesiology, Saitama Medical University International Medical Center, 1397-1, Yamane, Hidaka, Saitama 350-1298, Japan.
authors.forename: Kazushi
authors.initials: K
authors.lastname: Itoh
authors.affiliation: Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, 2-1-6, Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan.|Department of Anesthesiology & Pain Medicine, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Kojiro
authors.initials: K
authors.lastname: Amano
authors.affiliation: Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, 1397-1, Yamane, Hidaka, Saitama 350-1298, Japan.
authors.forename: Jo
authors.initials: J
authors.lastname: Tashiro
authors.affiliation: Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, 1397-1, Yamane, Hidaka, Saitama 350-1298, Japan.
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Ishii
authors.affiliation: Department of Anesthesiology, Saitama Medical University International Medical Center, 1397-1, Yamane, Hidaka, Saitama 350-1298, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Ariyama
authors.affiliation: Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, 1397-1, Yamane, Hidaka, Saitama 350-1298, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Yamaguchi
authors.affiliation: Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, 2-1-6, Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Kasai
authors.affiliation: Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, 2-1-6, Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Hasegawa
authors.affiliation: Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, 2-1-6, Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Ikeda
authors.affiliation: Department of Anesthesiology, Saitama Medical University International Medical Center, 1397-1, Yamane, Hidaka, Saitama 350-1298, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Kitamura
authors.affiliation: Department of Anesthesiology, Saitama Medical University International Medical Center, 1397-1, Yamane, Hidaka, Saitama 350-1298, Japan.|Department of Anesthesiology & Pain Medicine, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Hayashida
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000627:therapeutic use; D003082:Colectomy; D003110:Colonic Neoplasms / Q000235:genetics* / Q000601:surgery; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage* / Q000627:therapeutic use; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D010149:Postoperative Pain / Q000188:drug therapy*; D020641:Polymorphism, Single Nucleotide; D012004:Rectal Neoplasms / Q000235:genetics* / Q000601:surgery
chemical_list: D000701:Analgesics, Opioid; D005283:Fentanyl
keywords: analgesia; laparoscopic-assisted colectomy; opioids; pain; pharmacogenetics