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

ABSTRACT: BACKGROUND: 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. METHODS: 93 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. RESULTS: Association 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 (?) = 13.5 and p = 0.02, ? = 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, ? = 18.6); anxiety and depression (p = 0.008, ? = 15.4) and age (p = 0.03, mean difference per year (?) = 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. CONCLUSIONS: Results 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.

SUBMITTER: Omair A

PROVIDER: S-EPMC3453507 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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

Omair Ahmad A Lie Benedicte Alexandra BA Reikeras Olav O Holden Marit M Brox Jens Ivar JI

BMC musculoskeletal disorders 20120521

<h4>Background</h4>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 trea ...[more]

PMID: 22612913

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Project description:BackgroundInflammatory and matrix degrading gene variants have been reported to be associated with disc degeneration. Some of these variants also modulate peripheral pain. This study examines the association of these genetic variants with radiographic lumbar disc degeneration and changes in pain and disability at long-term after surgical and cognitive behavioural management.Methods93 unrelated patients with chronic low back pain (CLBP) for duration of >1 year and lumbar disc degeneration were treated with lumbar fusion or cognitive intervention and exercises. Standardised questionnaires included the Oswestry Disability Index (ODI) and Visual Analog Score (VAS) for CLBP, were filled in by patients both at baseline and at 9 years follow-up. Degenerative changes at baseline Magnetic Resonance Imaging and Computed Tomography scans, were graded as moderate and severe (N=79). Yield and quality of blood and saliva DNA was assessed by nano drop spectrophotometry. Eight SNPs in 5 inflammatory and matrix degrading genes were successfully genotyped. Single marker and haplotype association with severity of degeneration, number of discs involved, changes in ODI and VAS CLBP, was done using Haploview, linear regression and R-package Haplostats.ResultsAssociation analysis of individual SNPs revealed association of IL18RAP polymorphism rs1420100 with severe degeneration (p = 0.05) and more than one degenerated disc (p = 0.02). From the same gene two SNPs, rs917997 and rs1420106, were found to be in strong linkage disequilibrium (LD) and were associated with post treatment improvement in disability (p = 0.02). Haplotype association analysis of 5 SNPs spanning across IL18RAP, IL18R1 and IL1A genes revealed significant associations with improvement in disability (p=0.02) and reduction in pain (p=0.04). An association was found between MMP3 polymorphism rs72520913 and improvement in pain (p = 0.03) and with severe degeneration (p = 0.006).ConclusionsThe findings of the current study suggest a role of variation at inflammatory and matrix degrading genes with severity of lumbar disc degeneration, pain and disability.

Project description:ObjectivesContextual components of treatment previously associated with patient outcomes include the environment, therapeutic relationship and expectancies. Questions remain about which components are most important, how they influence outcomes and comparative effects across treatment approaches. We aimed to identify significant and strong contextual predictors of patient outcomes, test for psychological mediators and compare effects across three treatment approaches.DesignProspective cohort study with patient-reported and practitioner-reported questionnaire data (online or paper) collected at first consultation, 2 weeks and 3 months.SettingPhysiotherapy, osteopathy and acupuncture clinics throughout the UK.Participants166 practitioners (65 physiotherapists, 46 osteopaths, 55 acupuncturists) were recruited via their professional organisations. Practitioners recruited 960 adult patients seeking treatment for low back pain (LBP).Primary and secondary outcomesThe primary outcome was back-related disability. Secondary outcomes were pain and well-being. Contextual components measured were: therapeutic alliance; patient satisfaction with appointment systems, access, facilities; patients' treatment beliefs including outcome expectancies; practitioners' attitudes to LBP and practitioners' patient-specific outcome expectancies. The hypothesised mediators measured were: patient self-efficacy for pain management; patient perceptions of LBP and psychosocial distress.ResultsAfter controlling for baseline and potential confounders, statistically significant predictors of reduced back-related disability were: all three dimensions of stronger therapeutic alliance (goal, task and bond); higher patient satisfaction with appointment systems; reduced patient-perceived treatment credibility and increased practitioner-rated outcome expectancies. Therapeutic alliance over task (ηp 2=0.10, 95% CI 0.07 to 0.14) and practitioner-rated outcome expectancies (ηp 2=0.08, 95% CI 0.05 to 0.11) demonstrated the largest effect sizes. Patients' self-efficacy, LBP perceptions and psychosocial distress partially mediated these relationships. There were no interactions with treatment approach.ConclusionsEnhancing contextual components in musculoskeletal healthcare could improve patient outcomes. Interventions should focus on helping practitioners and patients forge effective therapeutic alliances with strong affective bonds and agreement on treatment goals and how to achieve them.

Dataset Information

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

Publications

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

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