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

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.