Polygenic mechanisms underpinning the response to exercise‐induced muscle damage in humans: In vivo and in vitro evidence

Abstract

We investigated whether 20 candidate single nucleotide polymorphisms (SNPs) were associated with in vivo exercise‐induced muscle damage (EIMD), and with an in vitro skeletal muscle stem cell wound healing assay. Sixty‐five young, untrained Caucasian adults performed 120 maximal eccentric knee‐extensions on an isokinetic dynamometer to induce EIMD. Maximal voluntary isometric/isokinetic knee‐extensor torque, knee joint range of motion (ROM), muscle soreness, serum creatine kinase activity and interleukin‐6 concentration were assessed before, directly after and 48 h after EIMD. Muscle stem cells were cultured from vastus lateralis biopsies from a separate cohort (n = 12), and markers of repair were measured in vitro. Participants were genotyped for all 20 SNPs using real‐time PCR. Seven SNPs were associated with the response to EIMD, and these were used to calculate a total genotype score, which enabled participants to be segregated into three polygenic groups: ‘preferential’ (more ‘protective’ alleles), ‘moderate’, and ‘non‐preferential’. The non‐preferential group was consistently weaker than the preferential group (1.93 ± 0.81 vs. 2.73 ± 0.59 N ∙ m/kg; P = 9.51 × 10−4) and demonstrated more muscle soreness (p = 0.011) and a larger decrease in knee joint ROM (p = 0.006) following EIMD. Two TTN‐AS1 SNPs in linkage disequilibrium were associated with in vivo EIMD (rs3731749, p ≤ 0.005) and accelerated muscle stem cell migration into the artificial wound in vitro (rs1001238, p ≤ 0.006). Thus, we have identified a polygenic profile, linked with both muscle weakness and poorer recovery following EIMD. Moreover, we provide evidence for a novel TTN gene‐cell‐skeletal muscle mechanism that may help explain some of the interindividual variability in the response to EIMD.

Blueberry intake elevates post-exercise anti-inflammatory oxylipins: a randomized trial

“…Changes in muscle damage biomarkers such as creatine kinase and myoglobin following eccentric exercise are highly variable between individuals as confirmed in this study. The underlying mechanisms explaining this variance is poorly understood but may be due to part to single nucleotide polymorphisms (SNPs) 37 . Interindividual variability in biomarker responses to eccentric exercise-induced muscle damage due to SNPs may limit the efficacy of nutritional interventions.…”

Association of the MuRF-1/TRIM63 polymorphism with muscle injuries in professional soccer players

“…This gene has been linked to situations such as muscle atrophy (Baehr et al, 2021), cardiomyopathies (Chen et al, 2012), and exercise-induced muscle damage (Baumert et al, 2022). Concerning exercise, researchers investigated this protein during endurance and resistance activities found that MuRF-1 mRNA protein levels increased significantly after endurance training and exercise (Baumert et al, 2022;Stefanetti et al, 2014). These studies showed consistent results revealing that the MuRF-1/TRIM63 response to exercise results in upregulation.…”

“…Genetic polymorphisms have been associated with non-contact muscle injuries in soccer (Lim et al, 2021, Maestro et al, 2022. In this context, evidence indicates that certain genetic polymorphisms, such as MuRF-1/TRIM63, may influence the mechanical properties of muscle fibers that express, for example, a phenotype with characteristics of delayed inflammation, resulting in slower recovery after exercise (Baumert et al, 2017;Baumert et al, 2022). The Muscle RING Finger-1 (MuRF-1) encoded by the human tripartite motif containing 63 (TRIM63) gene is located on chromosome 1 at position 26.058.512, in which a single nucleotide polymorphism (SNP, rs2275950; AA, AG and GG) at amino acid 237 causing a change from lysine to glutamate (Bodine et al, 2001;Centner et al, 2001).…”

“…A cluster of evidence has shown that MuRF-1/TRIM63 has been investigated as a regulator of muscle mass and is involved in catabolic processes identified in physiological conditions and pathological states (Peris-Moreno et al, 2020). This gene has been linked to situations such as muscle atrophy (Baehr et al, 2021), cardiomyopathies (Chen et al, 2012), and exercise-induced muscle damage (Baumert et al, 2022). Concerning exercise, researchers investigated this protein during endurance and resistance activities found that MuRF-1 mRNA protein levels increased significantly after endurance training and exercise (Baumert et al, 2022;Stefanetti et al, 2014).…”

Effect of High-Intensity vs. Moderate-Intensity Resistance Training on Strength, Power, and Muscle Soreness in Male Academy Soccer Players

“…Throughout the intervention, subjects were asked to report subjective muscle soreness for the lower limbs before, immediately after, 24 hours after, and 48 hours after each training session using a visual analog scale (VAS). The scale ranged from 0 cm, referring to no soreness, up to 10 cm, which would indicate extreme muscle soreness (1). At the 24 and 48 hours posttraining time points, subjects reported their lower-body muscle soreness using a Google form using the same standard VAS.…”