Polygenic mechanisms underpinning the response to exercise-induced muscle damage in humans: In vivo and in vitro evidence (2024)

Baumert, P., co*cks, M., Strauss, J. A., Shepherd, S. O., Drust, B., Lake, M. J., Stewart, C. E., & Erskine, R. M. (2022). Polygenic mechanisms underpinning the response to exercise-induced muscle damage in humans: In vivo and in vitro evidence. Journal of Cellular Physiology, 237(7), 2862-2876. Advance online publication. https://doi.org/10.1002/jcp.30723

Baumert, Philipp ; co*cks, Matthew ; Strauss, Juliette A. et al. / Polygenic mechanisms underpinning the response to exercise-induced muscle damage in humans : In vivo and in vitro evidence. In: Journal of Cellular Physiology. 2022 ; Vol. 237, No. 7. pp. 2862-2876.

@article{4b81b9939c334dc8b406d2bd5da3f036,

title = "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: {\textquoteleft}preferential{\textquoteright} (more {\textquoteleft}protective{\textquoteright} alleles), {\textquoteleft}moderate{\textquoteright}, and {\textquoteleft}non-preferential{\textquoteright}. 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.",

keywords = "eccentric exercise, extracellular matrix (ECM), fibroblast, myoblast, single-nucleotide polymorphism (SNP), total genotype score (TGS)",

author = "Philipp Baumert and Matthew co*cks and Strauss, {Juliette A.} and Shepherd, {Sam O.} and Barry Drust and Lake, {Mark J.} and Stewart, {Claire E.} and Erskine, {Robert M.}",

note = "Funding Information: We are very grateful to Bethany Adams, Josephine Cabot, Victoria Edwards, Kelsie Johnson and Matthew Stanley for their help with data collection. This study was supported by a Leonardo da Vinci Grant (EAC/S07/2012) and partly by the EuroTech Postdoc Programme (Grant Agreement number 754462), co‐funded by the European Commission under its framework programme Horizon 2020 (both P.B.), and by a Wellcome Trust Biomedical Vacation Scholarship (207194/Z/17/Z; R.M.E.). Open access funding enabled and organized by Projekt DEAL. Publisher Copyright: {\textcopyright} 2022 The Authors. Journal of Cellular Physiology published by Wiley Periodicals LLC.",

year = "2022",

month = jul,

doi = "10.1002/jcp.30723",

language = "English",

volume = "237",

pages = "2862--2876",

journal = "Journal of Cellular Physiology",

issn = "0021-9541",

publisher = "Wiley",

number = "7",

}

Baumert, P, co*cks, M, Strauss, JA, Shepherd, SO, Drust, B, Lake, MJ, Stewart, CE & 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, vol. 237, no. 7, pp. 2862-2876. https://doi.org/10.1002/jcp.30723

Polygenic mechanisms underpinning the response to exercise-induced muscle damage in humans: In vivo and in vitro evidence. / Baumert, Philipp; co*cks, Matthew; Strauss, Juliette A. et al.
In: Journal of Cellular Physiology, Vol. 237, No. 7, 07.2022, p. 2862-2876.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Polygenic mechanisms underpinning the response to exercise-induced muscle damage in humans

T2 - In vivo and in vitro evidence

AU - Baumert, Philipp

AU - co*cks, Matthew

AU - Strauss, Juliette A.

AU - Shepherd, Sam O.

AU - Drust, Barry

AU - Lake, Mark J.

AU - Stewart, Claire E.

AU - Erskine, Robert M.

N1 - Funding Information:We are very grateful to Bethany Adams, Josephine Cabot, Victoria Edwards, Kelsie Johnson and Matthew Stanley for their help with data collection. This study was supported by a Leonardo da Vinci Grant (EAC/S07/2012) and partly by the EuroTech Postdoc Programme (Grant Agreement number 754462), co‐funded by the European Commission under its framework programme Horizon 2020 (both P.B.), and by a Wellcome Trust Biomedical Vacation Scholarship (207194/Z/17/Z; R.M.E.). Open access funding enabled and organized by Projekt DEAL. Publisher Copyright:© 2022 The Authors. Journal of Cellular Physiology published by Wiley Periodicals LLC.

PY - 2022/7

Y1 - 2022/7

N2 - 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.

AB - 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.

KW - eccentric exercise

KW - extracellular matrix (ECM)

KW - fibroblast

KW - myoblast

KW - single-nucleotide polymorphism (SNP)

KW - total genotype score (TGS)

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U2 - 10.1002/jcp.30723

DO - 10.1002/jcp.30723

M3 - Article

C2 - 35312042

AN - SCOPUS:85126763520

SN - 0021-9541

VL - 237

SP - 2862

EP - 2876

JO - Journal of Cellular Physiology

JF - Journal of Cellular Physiology

IS - 7

ER -

Baumert P, co*cks M, Strauss JA, Shepherd SO, Drust B, Lake MJ et al. Polygenic mechanisms underpinning the response to exercise-induced muscle damage in humans: In vivo and in vitro evidence. Journal of Cellular Physiology. 2022 Jul;237(7):2862-2876. Epub 2022 Mar 21. doi: 10.1002/jcp.30723