Analgesic Requirements After Major Abdominal Surgery are Associated with
            <i>OPRM1</i>
            Gene Polymorphism Genotype and Haplotype

Hayashida, Masakazu; Nagashima, Makoto; Satoh, Yasuo; Katoh, Ryoji; Tagami, Minoru; Ide, Soichiro; Kasai, Shinya; Nishizawa, Daisuke; Ogai, Yasukazu; Hasegawa, Junko; Komatsu, Hiroshi; Sora, Ichiro; Fukuda, Ken‐ichi; Koga, Hisashi; Hanaoka, Kazuo; Ikeda, Kazutaka

doi:10.2217/14622416.9.11.1605

Cited by 132 publications

(93 citation statements)

References 43 publications

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“…Our study in newborn infants illustrated an increased risk for rescue analgesia with morphine while being on the ventilator in carriers of the OPRM1 118G allele in combination with the COMT 472GG genotype (52 ). A Japanese cohort with adult patients undergoing major abdominal surgery assessed 5 tag SNPs (118AϾG, IVS2 ϩ 691GϾC; rs2075572, IVS3 ϩ 5953GϾA; rs599548, IVS3 ϩ 8449AϾG, TAAϩ2109AϾG), of which only 118AϾG was significantly associated with opioid consumption (53 ). In summary, based on the extensive literature, the 118AϾG variant seems to be a potential biomarker for use in clinical practice.…”

Section: Oprm1mentioning

confidence: 89%

Analgesia and Opioids: A Pharmacogenetics Shortlist for Implementation in Clinical Practice

et al. 2017

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BACKGROUND The use of opioids to alleviate pain is complicated by the risk of severe adverse events and the large variability in dose requirements. Pharmacogenetics (PGx) could possibly be used to tailor pain medication based on an individual's genetic background. Many potential genetic markers have been described, and the importance of genetic predisposition in opioid efficacy and toxicity has been demonstrated in knockout mouse models and human twin studies. Such predictors are especially of value for neonates and young children, in whom the assessment of efficacy or side effects is complicated by the inability of the patient to communicate this properly. The current problem is determining which of the many potential candidates to focus on for clinical implementation. CONTENT We systematically searched publications on PGx for opioids in 5 databases, aiming to identify PGx markers with sufficient robust data and high enough occurrence for potential clinical application. The initial search yielded 4257 unique citations, eventually resulting in 852 relevant articles covering 24 genes. From these genes, we evaluated the evidence and selected the most promising 10 markers: cytochrome P450 family 2 subfamily D member 6 (CYP2D6), cytochrome P450 family 3 subfamily A member 4 (CYP3A4), cytochrome P450 family 3 subfamily A member 5 (CYP3A5), UDP glucuronosyltransferase family 2 member B7 (UGT2B7), ATP binding cassette subfamily B member 1 (ABCB1), ATP binding cassette subfamily C member 3 (ABCC3), solute carrier family 22 member 1 (SLC22A1), opioid receptor kappa 1 (OPRM1), catechol-O-methyltransferase (COMT), and potassium voltage-gated channel subfamily J member 6 (KCNJ6). Treatment guidelines based on genotype are already available only for CYP2D6. SUMMARY The application of PGx in the management of pain with opioids has the potential to improve therapy. We provide a shortlist of 10 genes that are the most promising markers for clinical use in this context.

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Section: Oprm1mentioning

confidence: 89%

Analgesia and Opioids: A Pharmacogenetics Shortlist for Implementation in Clinical Practice

et al. 2017

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“…In Caucasian populations the effect has been smaller or non-existent. 4,11,21,40 The GG genotype is much rarer in the Caucasian population 21,26,40 compared with the Asian population 10,19,31 which may explain some of the difference. In addition, many of the negative studies have had small sample sizes 4, 9, 11 or a low frequency of the G-allele.…”

Section: Multiple Linear Regression Modelsmentioning

confidence: 99%

How Much Oxycodone Is Needed for Adequate Analgesia After Breast Cancer Surgery: Effect of the OPRM1 118A>G Polymorphism

Cajanus

Kaunisto

Tallgren

et al. 2014

The Journal of Pain

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“…However, in contrast, the women carrying the 118G allele seem to report more pain than the women homozygous for the 118A the first 24 h after a cesarean operation (Sia et al, 2008;Tan et al, 2009). In addition, evidence exist that carriers of the OPRM1 118G allele may require higher doses of morphine in the early postoperative period (Klepstad et al, 2004;Chou et al, 2006;Hayashida et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Pain Intensity the First Year after Lumbar Disc Herniation Is Associated with the A118G Polymorphism in the Opioid Receptor Mu 1 Gene: Evidence of a Sex and Genotype Interaction

Olsen¹,

Jacobsen²,

Schistad³

et al. 2012

Journal of Neuroscience

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Earlier studies have shown that the single nucleotide polymorphism (SNP) A118G (rs1799971) in the opioid receptor mu 1 (OPRM1) gene may affect pain sensitivity. In the present study we investigated whether the A118G SNP could predict clinical outcome regarding progression of pain intensity and disability in patients with low back pain and sciatica after lumbar disc herniation. Patients (n ϭ 258) with lumbar disc herniation and sciatic pain, all European-Caucasian, were recruited from two hospitals in Norway. Pain and disability were rated on a visual analog scale (VAS), by McGill Sensory Questionnaire and by Oswestry Disability Index (ODI) over a 12 months period. The data revealed a significant interaction between sex and A118G genotype regarding the pain intensity during the 12 months (VAS, p ϭ 0.002; McGill, p ϭ 0.021; ODI, p ϭ 0.205, repeated-measures ANOVA). We found that */G women had a slower recovery rate than the */G men. Actually, the */G women had 2.3 times as much pain as the */G men 12 months after the disc herniation (VAS, p ϭ 0.043, one-way ANOVA; p ϭ 0.035, Tukey HSD). In contrast, the A/A women and A/A men seemed to have almost exactly the same recovery rate. The present data suggest that OPRM1 G allele increases the pain intensity in women, but has a protective effect in men the first year after disc herniation.

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Analgesic Requirements After Major Abdominal Surgery are Associated with OPRM1 Gene Polymorphism Genotype and Haplotype

Abstract: These results suggest that OPRM1 gene tag SNP genotypes and haplotypes can primarily contribute to prediction of postoperative analgesic requirements in individual patients undergoing major open abdominal surgery.

Cited by 132 publications

References 43 publications

Analgesia and Opioids: A Pharmacogenetics Shortlist for Implementation in Clinical Practice

Analgesia and Opioids: A Pharmacogenetics Shortlist for Implementation in Clinical Practice

How Much Oxycodone Is Needed for Adequate Analgesia After Breast Cancer Surgery: Effect of the OPRM1 118A>G Polymorphism

Pain Intensity the First Year after Lumbar Disc Herniation Is Associated with the A118G Polymorphism in the Opioid Receptor Mu 1 Gene: Evidence of a Sex and Genotype Interaction

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