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 (>= 60 years), overweight (body mass index >= 8 kg/m2) 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 = 0.05). Both walking distance (p = 0.02) and stair-climb time (p = 0.003) 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 = 0.02), and stair-climb time tended to be better (p = 0.06), 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 = 0.007), and on 18-month changes in self-reported physical disability (p = 0.01), 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.
Copyright the Gerontological Society of America. Reproduced by permission of the publisher.

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