Polygenic mechanisms underpinning the response to exercise-induced muscle damage in humans: In vivo and in vitro evidence.
Level 3 - non-randomized controlled study
Prospective cohort study assessing genetic associations with exercise responses, paired with in vitro assays.
PubMed 35312042 · doi:10.1002/jcp.30723
What was done
Sixty-five young, untrained Caucasian adults performed 120 maximal eccentric knee extensions on an isokinetic dynamometer to induce exercise-induced muscle damage (EIMD). Maximal voluntary isometric and isokinetic knee-extensor torque, knee joint range of motion (ROM), muscle soreness, serum creatine kinase activity, and interleukin-6 concentration were measured before, immediately after, and 48 hours post-exercise. Participants were genotyped for 20 candidate single nucleotide polymorphisms (SNPs) using real-time PCR. Muscle stem cells were cultured from vastus lateralis biopsies from a separate cohort (n = 12) for in vitro wound-healing assays.
What was found
Seven of 20 SNPs were associated with EIMD response and combined into a total genotype score ('preferential', 'moderate', 'non-preferential'). The non-preferential group showed lower post-damage strength than the preferential group (1.93 ± 0.81 vs. 2.73 ± 0.59 N·m/kg; p = 9.51 × 10⁻⁴), increased muscle soreness (p = 0.011), and a larger decrease in knee ROM (p = 0.006). Two linked TTN-AS1 SNPs were associated with in vivo EIMD (rs3731749, p ≤ 0.005) and accelerated stem cell migration into the artificial wound in vitro (rs1001238, p ≤ 0.006).
Why it matters
The study identifies a candidate polygenic profile and a TTN-AS1 regulatory mechanism that may contribute to individual differences in muscle damage susceptibility and recovery kinetics following eccentric exercise.
Limits
The study evaluated a modest sample (n = 65) restricted to young, untrained Caucasian individuals, limiting generalizability to other ancestries, age groups, or trained athletes. It used a candidate-gene approach rather than a genome-wide scan, without independent replication. The in vitro mechanistic work was conducted on a separate, small cohort (n = 12) rather than the exercise participants.
Cited by
- supports Individual differences in exercise enjoyment, pain tolerance, and muscle damage recovery have measurable genetic bases.