Human Genetic Variability Contributes to Postoperative Morphine Consumption

被引：50

作者：

De Gregori, Manuela ^{[1
,2
,3
]}

Diatchenko, Luda ^{[2
,4
]}

Ingelmo, Pablo M. ^{[2
,5
]}

Napolioni, Valerio ^{[2
,6
]}

Klepstad, Pal ^{[2
,7
,8
]}

Belfer, Inna ^{[2
,9
]}

Molinaro, Valeria ^{[10
]}

Garbin, Giulia ^{[10
]}

Ranzani, Guglielmina N. ^{[10
]}

Alberio, Giovanni ^{[13
]}

Normanno, Marco ^{[13
]}

Lovisari, Federica ^{[13
]}

Somaini, Marta ^{[13
]}

Govoni, Stefano ^{[2
,11
]}

Mura, Elisa ^{[11
]}

Bugada, Dario ^{[2
,12
]}

Niebel, Thekla ^{[2
,12
]}

Zorzetto, Michele ^{[14
]}

De Gregori, Simona ^{[15
]}

Molinaro, Mariadelfina ^{[15
]}

Fanelli, Guido ^{[2
,16
,17
]}

Allegri, Massimo ^{[2
,16
,17
]}

机构：

[1] Fdn IRCCS Policlin San Matteo, Pain Therapy Serv, Pavia, Italy

[2] Azienda Osped Univ Parma, SIMPAR Study Multidisciplinary Pain Res Grp, UO Anestesia Rianimaz & Terapia Antalg 2a, Parma, Italy

[3] Azienda Osped Univ Parma, YAP Young Pain Grp, UO Anestesia Rianimaz & Terapia Antalg 2a, Parma, Italy

[4] McGill Univ, Alan Edwards Pain Ctr Res Pain, Montreal, PQ, Canada

[5] Montreal Childrens Hosp, Dept Anesthesia, Montreal, PQ H3H 1P3, Canada

[6] Stanford Univ, Sch Med, Dept Neurol & Neurol Sci, Palo Alto, CA 94304 USA

[7] Norwegian Univ Sci & Technol NTNU, Dept Circulat & Med Imaging, Trondheim, Norway

[8] St Olavs Univ Hosp, Dept Anesthesiol & Intens Care Med, Trondheim, Norway

[9] Univ Pittsburgh, Dept Anesthesiol, Pittsburgh, PA USA

[10] Univ Parma, Dept Biol & Biotechnol, I-43126 Parma, Italy

[11] Univ Parma, Dept Expt & Appl Pharmacol, I-43126 Parma, Italy

[12] Univ Parma, Dept Clin Surg Pediat & Diagnost Sci, I-43126 Parma, Italy

[13] Azienda Osped San Gerardo, Serv Anesthesia 1, Monza, Italy

[14] Fdn IRCCS Policlin San Matteo, Lab Biochem & Genet, Div Pneumol, Dept Mol Med, Pavia, Italy

[15] Fdn IRCCS Policlin San Matteo, Clin & Expt Pharmacokinet Unit, Pavia, Italy

[16] Univ Parma, Dept Surg Sci, Anesthesia Crit Care & Pain Med, I-43126 Parma, Italy

[17] Azienda Osped Univ Parma, UO Anestesia Rianimaz & Terapia Antalg 2a, Parma, Italy

来源：

JOURNAL OF PAIN | 2016年 / 17卷 / 05期

关键词：

Acute postoperative pain; genetic variability; postoperative opioid consumption; genetic variants combination; OPRM1; haplotype; O-METHYLTRANSFERASE POLYMORPHISMS; OPIOID RECEPTOR GENE; PAIN PERCEPTION; OPRM1; ASSOCIATION; ANALGESIA; UGT2B7; REQUIREMENTS; SURGERY; A118G;

D O I：

10.1016/j.jpain.2016.02.003

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

High interindividual variability in postoperative opioid consumption is related to genetic and environmental factors. We tested the association between morphine consumption, postoperative pain, and single nucleotide polymorphisms (SNPs) within opioid receptor mu 1 (OPRM1), catechol-O-methyltransferase (COMT), uridine diphosphate glucose-glucuronosyltransferase-2B7, and estrogen receptor (ESR1) gene loci to elucidate genetic prediction of opioid consumption. We analyzed 20 SNPs in 201 unrelated Caucasian patients who underwent abdominal surgery and who were receiving postoperative patient-controlled analgesia-administered morphine. Morphine consumption and pain intensity were dependent variables; age and sex were covariates. A haplotype of 7 SNPs in OPRM1 showed significant additive effects on opioid consumption (P = .007); a linear regression model including age and 9 SNPs in ESR1, OPRM1, and COMT explained the highest proportion of variance of morphine consumption (10.7%; P = .001). The minimal model including 3 SNPs in ESR1, OPRM1, and COMT explained 5% of variance (P = .007). We found a significant interaction between rs4680 in COMT and rs4986936 in ESR1 (P = .007) on opioid consumption. SNPs rs677830 and rs540825 of OPRM1 and rs9340799 of ESR1 were nominally associated with pain Numeric Rating Scale scores. Combinations of genetic variants within OPRM1, COMT, and ESR1 better explain variability in morphine consumption than single genetic variants. Our results contribute to the development of genetic markers and statistical models for future diagnostic tools for opioid consumption/efficacy. (C) 2016 by the American Pain Society

引用

页码：628 / 636

页数：9

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