Physical function and its response to exercise: associations with cytokine gene variation in older adults with knee osteoarthritis

J Gerontol A Biol Sci Med Sci. 2005 Oct;60(10):1292-8. doi: 10.1093/gerona/60.10.1292.


Background: We determined whether physical function and its response to exercise training are associated with polymorphisms in cytokine genes (interleukin-6 [IL-6] -174 G/C; tumor necrosis factor alpha [TNFalpha] -308 G/A and -238 G/A; and TNFalpha receptors [TNFR]1 +36 A/G, TNFR2 +676 T/G, and TNFR2 +1663 A/G), in 214 older (> or =60 years), overweight (body mass index > or =28 kg/m(2)) individuals with knee osteoarthritis.

Methods: Physical function (walking distance, stair-climb time, self-reported disability) was measured before and after an 18-month randomized, controlled exercise trial involving walking and weight lifting 3 days/week.

Results: In cross-sectional analyses, baseline walking distance was greater in individuals homozygous for the major G allele at IL-6 -174 compared to individuals with at least one C allele (p = .05). Both walking distance (p =.02) and stair-climb time (p = .003) were better in individuals homozygous for the major G allele of the TNFalpha -308 polymorphism compared to those with at least one A allele. Walking distance was better (p = .02), and stair-climb time tended to be better (p = .06), in individuals homozygous for the major T allele of the TNFR2 +676 polymorphism. No associations were seen with self-reported physical disability nor with the other polymorphisms. In response to exercise, there was a significant interaction between TNFalpha -308 genotype and exercise treatment on 6-month changes in stair-climb time (p = .007), and on 18-month changes in self-reported physical disability (p = .01), such that individuals with an A allele showed greater improvement in response to exercise.

Conclusions: Walking distance and stair climbing speed are partly influenced by genetic variation in the IL-6 and TNFalpha genes in older individuals with knee osteoarthritis.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Alleles
  • Cytokines / genetics*
  • Exercise*
  • Female
  • Genetic Variation
  • Humans
  • Interleukin-6 / genetics
  • Male
  • Motor Activity / genetics*
  • Osteoarthritis, Knee / physiopathology*
  • Tumor Necrosis Factor-alpha / genetics
  • Walking
  • Weight Lifting


  • Cytokines
  • Interleukin-6
  • Tumor Necrosis Factor-alpha