title: Physical function and its response to exercise: associations with cytokine gene variation in older adults with knee osteoarthritis.
abstract: 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.
authors.affiliation: Sticht Center on Aging, Section on Gerontology and Geriatric Medicine, Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA. bnicklas@wfubmc.edu
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Nicklas
authors.forename: Joe
authors.initials: J
authors.lastname: Mychaleckyj
authors.forename: Stephen
authors.initials: S
authors.lastname: Kritchevsky
authors.forename: Shana
authors.initials: S
authors.lastname: Palla
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Lange
authors.forename: Ethan M
authors.initials: EM
authors.lastname: Lange
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Messier
authors.forename: Don
authors.initials: D
authors.lastname: Bowden
authors.forename: Marco
authors.initials: M
authors.lastname: Pahor
mesh_terms: D000368:Aged; D000483:Alleles; D016207:Cytokines / Q000235:genetics*; D015444:Exercise; D005260:Female; D014644:Genetic Variation; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics; D008297:Male; D009043:Motor Activity / Q000235:genetics*; D020370:Osteoarthritis, Knee / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D016138:Walking; D014891:Weight Lifting
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha