title: Ethnicity-dependent influence of innate immune genetic markers on morphine PCA requirements and adverse effects in postoperative pain.
abstract: Although several genetic factors have been associated with postsurgical morphine requirements, those involving the innate immune system and cytokines have not been well investigated. The aim of this study was to investigate the contribution of genetic variability in innate immune signalling pathways to variability in morphine dosage after elective caesarean section under spinal anaesthesia in 133 Indian, 230 Malay, and 598 Han Chinese women previously studied. Twenty single nucleotide polymorphisms in 14 genes involved in glial activation (TLR2, TLR4, MYD88, MD2), inflammatory signalling (IL2, IL6, IL10, IL1B, IL6R, TNFA, TGFB1, CRP, CASP1), and neuronal regulation (BDNF) were newly investigated, in addition to OPRM1, COMT, and ABCB1 genetic variability identified previously. Postsurgical patient-controlled analgesia morphine use (mg/24 hours) was binned into 6 normally distributed groups and scored 0 to 5 to facilitate step-down multiple linear regression analysis of genetic predictors, controlling for ethnicity and nongenetic variables. Ethnicity, OPRM1 rs1799971 (increased), TLR2 rs3804100 (decreased), and an interaction between ethnicity and IL1B rs1143634 (increased), predicted 9.8% of variability in morphine use scores in the entire cohort. In the Indian cohort, 14.5% of the variance in morphine use score was explained by IL1B rs1143634 (increased) and TGFB1 rs1800469 (decreased). In Chinese patients, the incidence of postsurgical pain was significantly higher in variant COMT rs4680 genotypes (P = 0.0007) but not in the Malay or Indian cohorts. Innate immune genetics may contribute to variability in postsurgical opioid requirements in an ethnicity-dependent manner.
authors.affiliation: Discipline of Pharmacology, School of Medicine, Faculty of Health Sciences, University of Adelaide, Adelaide, South Australia, Australia.|Department of Clinical Pharmacology, Royal Adelaide Hospital, Adelaide, South Australia, Australia.
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Somogyi
authors.affiliation: KK Research Centre, KK Women's and Children's Hospital, Singapore.|Department of Women's Anesthesia, KK Women's and Children's Hospital, Singapore.
authors.forename: Alex T
authors.initials: AT
authors.lastname: Sia
authors.affiliation: KK Research Centre, KK Women's and Children's Hospital, Singapore.|Paediatrics Academic Clinical Programme, SingHealth Duke-NUS Graduate Medical School, Singapore.
authors.forename: Ene-Choo
authors.initials: EC
authors.lastname: Tan
authors.affiliation: Discipline of Pharmacology, School of Medicine, Faculty of Health Sciences, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Janet K
authors.initials: JK
authors.lastname: Coller
authors.affiliation: Discipline of Physiology, School of Medicine, Faculty of Health Sciences, University of Adelaide, Adelaide, South Australia, Australia.|Australian Research Council Centre of Excellence for Nanoscale BioPhotonics, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Hutchinson
authors.affiliation: Discipline of Pharmacology, School of Medicine, Faculty of Health Sciences, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Barratt
mesh_terms: D000293:Adolescent; D000328:Adult; D002394:Catechol O-Methyltransferase / Q000235:genetics; D015331:Cohort Studies; D005006:Ethnicity; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects* / Q000235:genetics*; D053583:Interleukin-1beta / Q000235:genetics; D016014:Linear Models; D008875:Middle Aged; D009020:Morphine / Q000627:therapeutic use*; D009294:Narcotics / Q000627:therapeutic use*; D010147:Pain Measurement; D010149:Postoperative Pain / Q000188:drug therapy / Q000208:ethnology / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D012846:Singapore / Q000208:ethnology; D053773:Transforming Growth Factor beta1 / Q000235:genetics; D055815:Young Adult
chemical_list: D053583:Interleukin-1beta; D009294:Narcotics; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D009020:Morphine; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase