Genetic contribution of catechol-O-methyltransferase variants in treatment outcome of low back pain: a prospective genetic association study

Ahmad Omair,Benedicte Alexandra Lie,Olav Reikeras,Marit Holden,Jens Ivar Brox

doi:10.1186/1471-2474-13-76

Ahmad Omair, Benedicte Alexandra Lie + Show 3 more

Open Access

https://doi.org/10.1186/1471-2474-13-76

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Abstract

BackgroundTreatment outcome of low back pain (LBP) is associated with inter-individual variations in pain relief and functional disability. Genetic variants of catechol-O-methyltransferase (COMT) gene have previously been shown to be associated with pain sensitivity and pain medication. This study examines the association between COMT polymorphisms and 7–11 year change in Oswestry Disability Index (ODI) and Visual Analog Score (VAS) for LBP as clinical outcome variables in patients treated with surgical instrumented lumbar fusion or cognitive intervention and exercise.Methods93 unrelated patients with chronic LBP for duration of >1 year and lumbar disc degeneration (LDD) were treated with lumbar fusion (N = 60) or cognitive therapy and exercises (N = 33). Standardised questionnaires assessing the ODI, VAS LBP, psychological factors and use of analgesics, were answered by patients both at baseline and at 7–11 years follow-up. Four SNPs in the COMT gene were successfully genotyped. Single marker as well as haplotype association with change in ODI and VAS LBP, were analyzed using Haploview, linear regression and R-package Haplostats. P-values were not formally corrected for multiple testing as this was an explorative study.ResultsAssociation analysis of individual SNPs adjusted for covariates revealed association of rs4633 and rs4680 with post treatment improvement in VAS LBP (p = 0.02, mean difference (β) = 13.5 and p = 0.02, β = 14.2 respectively). SNPs, rs4633 and rs4680 were found to be genotypically similar and in strong linkage disequilibrium (LD). A significant association was found with covariates, analgesics (p = 0.001, β = 18.6); anxiety and depression (p = 0.008, β = 15.4) and age (p = 0.03, mean difference per year (β) = 0.7) at follow-up. There was a tendency for better improvement among heterozygous patients compared to the homozygous. No association was observed for the analysis of the common haplotypes, these SNPs were situated on.ConclusionsResults suggest an influence of genetic variants of COMT gene in describing the variation in pain after treatment for low back pain. Replication in large samples with testing for other pain related genes is warranted.

Highlights

Treatment outcome of low back pain (LBP) is associated with inter-individual variations in pain relief and functional disability
With regard to the variation in human pain phenotypes, associations have been reported with single nucleotide polymorphisms (SNPs) in genes coding for catechol-O-methyltransferase (COMT), opioid receptors (OPRM1, OPRD1), transient receptor potential (TRPV1, TRPA1), fatty acid amide hydrolase (FAAH) and α-subunit of voltage gated sodium channel (SCN9A)[6,7,8,9,10,11]
In light of the broad spectrum of pain ratings in patients with Lumbar disc degeneration (LDD) treated for LBP, we aimed to investigate the effect of the genetic variation in COMT gene on the pain and disability scores among patients treated with lumbar instrumental fusion or cognitive intervention and exercises

Summary

Introduction

Treatment outcome of low back pain (LBP) is associated with inter-individual variations in pain relief and functional disability. Genetic variants of catechol-O-methyltransferase (COMT) gene have previously been shown to be associated with pain sensitivity and pain medication. This study examines the association between COMT polymorphisms and 7–11 year change in Oswestry Disability Index (ODI) and Visual Analog Score (VAS) for LBP as clinical outcome variables in patients treated with surgical instrumented lumbar fusion or cognitive intervention and exercise. With regard to the variation in human pain phenotypes, associations have been reported with single nucleotide polymorphisms (SNPs) in genes coding for catechol-O-methyltransferase (COMT), opioid receptors (OPRM1, OPRD1), transient receptor potential (TRPV1, TRPA1), fatty acid amide hydrolase (FAAH) and α-subunit of voltage gated sodium channel (SCN9A)[6,7,8,9,10,11]. COMT gene variations (more than 30 SNPs) are the most studied in both human and experimental models

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