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Please use this identifier to cite or link to this item: http://hdl.handle.net/11055/250
Title: Targeted Genotyping Identifies Susceptibility Locus in Brain-derived Neurotrophic Factor Gene for Chronic Postsurgical Pain.
Authors: Tian, Yuanyuan
Liu, Xiaodong
Jia, Mingzhong
Yu, Hui
Lichtner, Peter
Shi, Yujian
Meng, Zhaoyu
Kou, Shanglong
Ho, Idy H T
Jia, Bo
Cheng, Benny C P
Lam, CKM
Tsang, Sharon
Wong, Sunny H
Yu, Jun
Cheng, Christopher H K
Gin, T
Wu, William K K
Chen, Zheyu
Chan, MTV
ANZCA/FPM Author: Lam, CKM
Gin, Tony
Chan, MTV
Issue Date: Mar-2018
Citation: Anesthesiology 2018-03; 128(3): 587-597
Abstract: The purpose of this study was to evaluate the association between single-nucleotide polymorphisms and chronic postsurgical pain. Using GoldenGate genotyping assays, we genotyped 638 polymorphisms within 54 pain-related genes in 1,152 surgical patients who were enrolled in our Persistent Pain after Surgery Study. Patients were contacted by phone to determine whether they had chronic postsurgical pain at 12 months. Polymorphisms identified were validated in a matched cohort of 103 patients with chronic postsurgical pain and 103 patients who were pain free. The functions of targeted polymorphisms were tested in an experimental plantar incisional nociception model using knock-in mice. At 12 months after surgery, 246 (21.4%) patients reported chronic postsurgical pain. Forty-two polymorphisms were found to be associated with chronic postsurgical pain, 19 decreased the risk of pain, and 23 increased the risk of pain. Patients carrying allele A of rs6265 polymorphism in brain-derived neurotrophic factor (BDNF) had a lower risk of chronic postsurgical pain in the discovery and validation cohorts, with an adjusted odds ratio (95% CI) of 0.62 (0.43 to 0.90) and 0.57 (0.39 to 0.85), respectively. Age less than 65 yr, male sex, and prior history of pain syndrome were associated with an increased risk of pain. Genetic polymorphisms had higher population attributable risk (7.36 to 11.7%) compared with clinical risk factors (2.90 to 5.93%). Importantly, rs6265 is a substitution of valine by methionine at amino acid residue 66 (Val66Met) and was associated with less mechanical allodynia in BDNF mice compared with BDNF group after plantar incision. This study demonstrated that genetic variation of BDNF is associated with an increased risk of chronic postsurgical pain.
URI: http://hdl.handle.net/11055/250
DOI: 10.1097/ALN.0000000000001977
PubMed URL: https://www.ncbi.nlm.nih.gov/pubmed/29120944
Journal Title: Anesthesiology
Type: Journal Article
Appears in Collections:Scholarly and Clinical

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