Baumert, P, Cocks, MS, Strauss, JA, Shepherd, SO, Drust, B, Lake, MJ, Stewart, CE and Erskine, RM (2022) Polygenic Mechanisms Underpinning the Response to Exercise-Induced Muscle Damage in Humans: in vivo and in vitro Evidence. Journal of Cellular Physiology. ISSN 0021-9541

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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, muscle soreness, serum creatine kinase activity and interleukin-6 concentration were assessed before, directly after and 48h 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 (TGS), 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=9.51x10-4) and demonstrated more muscle soreness (P=0.011) and a larger decrease in knee joint range of motion (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 inter-individual variability in the response to EIMD.

Item Type:	Article
Uncontrolled Keywords:	0601 Biochemistry and Cell Biology, 1116 Medical Physiology
Subjects:	R Medicine > RC Internal medicine > RC1200 Sports Medicine
Divisions:	Sport & Exercise Sciences
Publisher:	Wiley
Date Deposited:	08 Mar 2022 14:34
Last Modified:	28 Mar 2022 14:45
DOI or ID number:	10.1002/jcp.30723
URI:	https://researchonline.ljmu.ac.uk/id/eprint/16463

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