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Ethnicity-dependent influence of innate immune genetic markers on morphine PCA requirements and adverse effects in postoperative pain

Somogyi, Andrew A.; Sia, Alex T.; Tan, Ene-Choo; Coller, Janet K.; Hutchinson, Mark R.; Barratt, Daniel T.

doi: 10.1097/j.pain.0000000000000661
Research Paper

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.

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aDiscipline of Pharmacology, School of Medicine, Faculty of Health Sciences, University of Adelaide, Adelaide, South Australia, Australia

bDepartment of Clinical Pharmacology, Royal Adelaide Hospital, Adelaide, South Australia, Australia

cKK Research Centre, KK Women's and Children's Hospital, Singapore

dDepartment of Women's Anesthesia, KK Women's and Children's Hospital, Singapore

ePaediatrics Academic Clinical Programme, SingHealth Duke-NUS Graduate Medical School, Singapore

fDiscipline of Physiology, School of Medicine, Faculty of Health Sciences, University of Adelaide, Adelaide, South Australia, Australia

gAustralian Research Council Centre of Excellence for Nanoscale BioPhotonics, University of Adelaide, Adelaide, South Australia, Australia

Corresponding author. Address: Discipline of Pharmacology, School of Medicine, Faculty of Health Sciences, University of Adelaide, Adelaide, South Australia, 5005 Australia. Tel.: +61 8 8313 5572; fax: +61 8 8224 0685. E-mail address: (A. A. Somogyi).

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (

Received March 25, 2016

Received in revised form June 26, 2016

Accepted July 05, 2016

© 2016 International Association for the Study of Pain
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