title: Treatment outcome of chronic low back pain and radiographic lumbar disc degeneration are associated with inflammatory and matrix degrading gene variants: a prospective genetic association study.
abstract: BACKGROUND
  Inflammatory 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.
  
  
  METHODS
  93 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.
  
  
  RESULTS
  Association 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).
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: Department of Orthopaedics, Oslo University Hospital-Rikshospitalet, Sognsvannsveien 20, Oslo 0027, Norway. ahmad.omair@ous-hf.no
authors.forename: Ahmad
authors.initials: A
authors.lastname: Omair
authors.forename: Marit
authors.initials: M
authors.lastname: Holden
authors.forename: Benedicte Alexandra
authors.initials: BA
authors.lastname: Lie
authors.forename: Olav
authors.initials: O
authors.lastname: Reikeras
authors.forename: Jens Ivar
authors.initials: JI
authors.lastname: Brox
mesh_terms: D000328:Adult; D059350:Chronic Pain / Q000000981:diagnostic imaging / Q000235:genetics* / Q000601:surgery; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D056726:Genetic Association Studies / Q000379:methods*; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000000981:diagnostic imaging / Q000235:genetics / Q000601:surgery; D018836:Inflammation Mediators / Q000502:physiology; D020382:Interleukin-18 / Q000235:genetics*; D055959:Intervertebral Disc Degeneration / Q000000981:diagnostic imaging / Q000235:genetics* / Q000601:surgery; D017116:Low Back Pain / Q000000981:diagnostic imaging / Q000235:genetics* / Q000601:surgery; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000601:surgery; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000235:genetics*; D008875:Middle Aged; D010147:Pain Measurement / Q000379:methods; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011446:Prospective Studies; D011859:Radiography; D013123:Spinal Fusion / Q000639:trends; D016896:Treatment Outcome
chemical_list: D018836:Inflammation Mediators; D020382:Interleukin-18; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3