A novel catechol-O-methyltransferase variant associated with human disc degeneration

Int J Med Sci. 2014 May 15;11(7):748-53. doi: 10.7150/ijms.8770. eCollection 2014.

Abstract

Background: Disc degeneration and its associated low back pain are a major health care concern causing disability with a prominent role in this country's medical, social and economic structure. Low back pain is devastating and influences the quality of life for millions. Low back pain lifetime prevalence approximates 80% with an estimated direct cost burden of $86 billion per year. Back pain patients incur higher costs, greater health care utilization, and greater work loss than patients without back pain.

Methods: Research was performed following approval of our Institutional Review Board. DNA was isolated, processed and amplified using routine techniques. Amplified DNA was hybridized to Affymetrix Genome-Wide Human SNP Arrays. Quality control and genotyping analysis were performed using Affymetrix Genotyping Console. The Birdseed v2 algorithm was used for genotyping analysis. 2589 SNPs were selected a priori to enter statistical analysis using lotistic regression in SAS.

Results: Our objective was to search for novel single nucleotide polymorphisms (SNPs) associated with disc degeneration. Four SNPs were found to have a significant relationship to disc degeneration; three are novel. Rs165656, a new SNP found to be associated with disc degeneration, was in catechol-O-methyltransferase (COMT), a gene with well-recognized pain involvement, especially in female subjects (p=0.01). Analysis confirmed the previously association between COMT SNP rs4633 and disc degeneration. We also report two novel disc degeneration-related SNPs (rs2095019 and rs470859) located in intergenic regions upstream to thrombospondin 2.

Conclusions: Findings contribute to the challenging field of disc degeneration and pain, and are important in light of the high clinical relevance of low back pain and the need for improved understanding of its fundamental basis.

Keywords: SNP; catechol-O-methyltransferase (COMT); low back pain..

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Catechol O-Methyltransferase / genetics*
  • Female
  • Genetic Association Studies
  • Humans
  • Intervertebral Disc Degeneration / complications
  • Intervertebral Disc Degeneration / genetics*
  • Intervertebral Disc Degeneration / pathology
  • Low Back Pain / complications
  • Low Back Pain / genetics*
  • Low Back Pain / pathology
  • Male
  • Middle Aged
  • Pain / complications
  • Pain / genetics*
  • Pain / pathology
  • Polymorphism, Single Nucleotide
  • Sex Characteristics

Substances

  • Catechol O-Methyltransferase