Myosin Light Chain Kinase (MLCK) Gene Influences Exercise Induced Muscle Damage during a Competitive Marathon

Abstract

Myosin light chain kinase (MLCK) phosphorylates the regulatory light chain (RLC) of myosin producing increases in force development during skeletal muscle contraction. It has been suggested that MLCK gene polymorphisms might alter RLC phosphorylation thereby decreasing the ability to produce force and to resist strain during voluntary muscle contractions. Thus, the genetic variations in the MLCK gene might predispose some individuals to higher values of muscle damage during exercise, especially during endurance competitions. The aim of this investigation was to determine the influence of MLCK genetic variants on exercise-induced muscle damage produced during a marathon. Sixty-seven experienced runners competed in a marathon race. The MLCK genotype (C37885A) of these marathoners was determined. Before and after the race, a sample of venous blood was obtained to assess changes in serum myoglobin concentrations and leg muscle power changes were measured during a countermovement jump. Self-reported leg muscle pain and fatigue were determined by questionnaires. A total of 59 marathoners (88.1%) were CC homozygotes and 8 marathoners (11.9%) were CA heterozygotes. The two groups of participants completed the race with a similar time (228 ± 33 vs 234 ± 39 min; P = 0.30) and similar self-reported values for fatigue (15 ± 2 vs 16 ± 2 A.U.; P = 0.21) and lower-limb muscle pain (6.2 ± 1.7 vs 6.6 ± 1.8 cm; P = 0.29). However, CC marathoners presented higher serum myoglobin concentrations (739 ± 792 vs 348 ± 144 μg·mL-1; P = 0.03) and greater pre-to-post- race leg muscle power reduction (-32.7 ± 15.7 vs -21.2 ± 21.6%; P = 0.05) than CA marathoners. CA heterozygotes for MLCK C37885A might present higher exercise-induced muscle damage after a marathon competition than CC counterparts.

Optimum polygenic profile to resist exertional rhabdomyolysis during a marathon

“…Age, main morphological and physical characteristics and running training habits and experience are depicted in Table 1 . The single influence of the SNPs associated to the MLCK gene [ 23 ] and the ACTN3 gene [ 26 ] on exercise-induced muscle damage in these same participants has been previously presented elsewhere.…”

“…Genotyping methods have been described elsewhere [ 23 ] and were in accordance with rigorous recommendations for replicating human genotype-phenotype association investigations. Briefly, genomic DNA was isolated from the whole blood obtained before the race (QIAamp ® DNA Blood Mini Kit, QIAGEN, The Netherlands) according to the manufacturer’s protocol and the genotyping was performed using a TaqMan ® SNP genotyping assay (Life Technologies ™ , USA) that employs the 5’ nuclease activity of Taq DNA polymerase to detect a fluorescent reporter signal generated during Real-Time PCR reactions.…”

“…The C37885A SNP of the MLCK gene and its influence on muscle damage has been studied with contradictory results. While it has been found that A-allele carriers for this MLCK SNP have greater muscle strength loss and increased plasma CK following eccentric contractions of the elbow flexor muscles [ 22 ], others have found that CA heterozygotes have fewer signs of muscle damage after a marathon than CC homozygotes [ 23 ]. Finally, tumor necrosis factor (TNFα) is a pro-inflammatory cytokine associated with the up-regulation of catabolic pathways and suppression of protein synthesis in skeletal muscle [ 24 ].…”

Methodological Approach of the Iron and Muscular Damage: Female Metabolism and Menstrual Cycle during Exercise Project (IronFEMME Study)

“…For the selection of SNP, we took into account their prevalence in the general population and/or their physiological impact and/or function. The potential roles for all of the selected variants were documented, and they were located in genes coding for proteins influencing the expression of the hepcidin gene (TMPRSS6, encoding for Matriptase-2) [ 72 , 73 , 74 ], iron metabolism and its regulation (HFE and TF) [ 72 , 75 , 76 , 77 , 78 ], proteins used as post-exercise muscle damage markers or involved in the response of exercise-induced muscle damage (ACTN3, CKMM, and MLCK) [ 79 , 80 , 81 , 82 , 83 , 84 ], or proteins related to the inflammatory response (IL6 and TNF) [ 85 , 86 , 87 , 88 , 89 , 90 ].…”

Atletik Performans ve Spor Genetiği

“…Ca2 + 'nin tropomiyosintroponine bağlanması ve iskelet kası kasılmasının birincil düzenleyicisidir. Bununla birlikte kuvvet gelişiminde de önemli bir role sahiptir [108]. Clarkson ve ark.…”