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Physical Function and Its Response to Exercise: Associations With Cytokine Gene Variation in Older Adults With Knee Osteoarthritis

¹ Sticht Center on Aging, Section on Gerontology and Geriatric Medicine, Department of Internal Medicine, ² Center for Human Genomics, and ³ Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
⁴ Department of Health and Exercise Sciences, Wake Forest University, Winston-Salem, North Carolina.

Address correspondence to Barbara J. Nicklas, PhD, J. Paul Sticht Center on Aging, Wake Forest University School of Medicine, Winston-Salem, NC 27157. E-mail: bnicklas{at}wfubmc.edu

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 [TNF] –308 G/A and –238 G/A; and TNF receptors [TNFR]1 +36 A/G, TNFR2 +676 T/G, and TNFR2 +1663 A/G), in 214 older (60 years), overweight (body mass index 28 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 =.05). Both walking distance (p =.02) and stair-climb time (p =.003) were better in individuals homozygous for the major G allele of the TNF –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 TNF –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 TNF genes in older individuals with knee osteoarthritis.