title: 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 (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.
  
  
  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.
authors.affiliation: Department of Orthopaedics, Oslo University Hospital-Rikshospitalet, Oslo, Norway. ahmad.omair@ous-hf.no
authors.forename: Ahmad
authors.initials: A
authors.lastname: Omair
authors.forename: Benedicte Alexandra
authors.initials: BA
authors.lastname: Lie
authors.forename: Olav
authors.initials: O
authors.lastname: Reikeras
authors.forename: Marit
authors.initials: M
authors.lastname: Holden
authors.forename: Jens Ivar
authors.initials: JI
authors.lastname: Brox
mesh_terms: D000328:Adult; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D004185:Disability Evaluation; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D055959:Intervertebral Disc Degeneration / Q000235:genetics / Q000503:physiopathology / Q000601:surgery; D015810:Linkage Disequilibrium / Q000235:genetics; D017116:Low Back Pain / Q000235:genetics* / Q000503:physiopathology / Q000601:surgery; D008159:Lumbar Vertebrae; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012107:Research Design; D013123:Spinal Fusion; D011795:Surveys and Questionnaires
chemical_list: D002394:Catechol O-Methyltransferase