Polygenic mechanisms underpinning the response to exercise‐induced muscle damage in humans: In vivo and in vitro evidence. Issue 7 (21st March 2022)

• Record Type: Journal Article
• Authors: Baumert, Philipp; Cocks, Matthew; Strauss, Juliette A.; Shepherd, Sam O.; Drust, Barry; Lake, Mark J.; Stewart, Claire E.; Erskine, Robert M.
• Is Part Of: Journal of cellular physiology. Volume 237:Issue 7(2022)
• Page Start: 2862
• Page End: 2876
• Publication Date: 2022-03-21
• Subjects: eccentric exercise -- extracellular matrix (ECM) -- fibroblast -- myoblast -- single‐nucleotide polymorphism (SNP) -- total genotype score (TGS); Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.30723
• Languages: English
• ISSNs: 0021-9541

Abstract

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. Abstract : The primary aim of this study was to investigate the polygenic association with exercise‐induced muscle damage (EIMD), and the objective was to determine if a combination of specific genetic variations could differentiate between high and low responders to EIMD. A second aim was to investigate whether those specific genetic variations associated with in vivo EIMD were also linked to the rate of repair in an in vitro human skeletal muscle stem cell wound healing assay, thus potentially elucidating novel mechanisms underpinning EIMD in vivo. Here, two genetic variations within the titin gene were associated with muscle soreness following EIMD in the in vivo study (single nucleotide polymorphism: rs3731749), and with total cell migration into the wound zone in the Muscle Stem Cell study (single nucleotide polymorphism: rs1001238), with both genetic variations being in high linkage disequilibrium