COL9A3 gene polymorphism and obesity in intervertebral disc degeneration of the lumbar spine: evidence of gene-environment interaction

Spine (Phila Pa 1976). 2002 Dec 1;27(23):2691-6. doi: 10.1097/00007632-200212010-00008.


Study design: Cross-sectional.

Objectives: To evaluate the interaction between the COL9A3 gene polymorphism and persistent obesity in relation to lumbar disc degeneration.

Summary of background data: Obesity has been suggested to be a risk factor for disc degeneration. There is some indication for an association between collagen IX genes and lumbar disc disease characterized by sciatica. However, the interaction between those factors in their influences on the risk of disc degeneration has not been studied.

Methods: Blood samples from 135 middle-aged men who had undergone magnetic resonance imaging (MRI) of the lumbar spine were analyzed for the presence of an arginine to tryptophan change in the COL9A3 gene (Trp3 allele). The men represented three occupations: 41 were machine drivers, 42 were carpenters, and 52 were office workers. The discs L2/L3-L5/S1 were evaluated on MRI, using decreased signal intensity of the nucleus pulposus, posterior disc bulges, and decreased disc height as signs of disc degeneration. Based on self-reports on body height and weight currently and at the age of 25 years, obesity history was classified as no obesity, persistent obesity, and other. Rothman's synergy index was used as a measure of interaction between two factors.

Results: The Trp3 allele and persistent obesity acted synergistically to increase the risk of dark nucleus pulposus, posterior disc bulge, and decreased disc height at L4/L5; of multilevel posterior disc bulges; and of decreased disc height. From 45% to 71% of disc degeneration among persistently obese individuals with the Trp3 allele could be attributed to the synergism of these two factors.

Conclusion: The effect of obesity on lumbar disc degeneration seems to be modified by the collagen IX gene polymorphism, so that people who carry the Trp3 allele are at increased risk if they are persistently obese.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Amino Acid Substitution
  • Body Mass Index
  • Chronic Disease
  • Cohort Studies
  • Collagen / genetics*
  • Collagen Type IX*
  • Comorbidity
  • Cross-Sectional Studies
  • Environment
  • Finland / epidemiology
  • Gene Frequency
  • Humans
  • Intervertebral Disc Displacement / diagnosis
  • Intervertebral Disc Displacement / epidemiology*
  • Intervertebral Disc Displacement / genetics*
  • Lumbosacral Region
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Obesity / diagnosis
  • Obesity / epidemiology*
  • Occupations
  • Odds Ratio
  • Polymorphism, Genetic / genetics*
  • Risk Assessment
  • Spine / pathology


  • COL9A3 protein, human
  • Collagen Type IX
  • Collagen