Department of Integrative Systems Biology, Research Center for Genetic Medicine, Children's National Medical Center, George Washington University, Washington, DC 20010, USA.
J Appl Physiol (1985). 2010 Dec;109(6):1779-85. doi: 10.1152/japplphysiol.00633.2010. Epub 2010 Oct 14.
Baseline muscle size and muscle adaptation to exercise are traits with high variability across individuals. Recent research has implicated several chemokines and their receptors in the pathogenesis of many conditions that are influenced by inflammatory processes, including muscle damage and repair. One specific chemokine, chemokine (C-C motif) ligand 2 (CCL2), is expressed by macrophages and muscle satellite cells, increases expression dramatically following muscle damage, and increases expression further with repeated bouts of exercise, suggesting that CCL2 plays a key role in muscle adaptation. The present study hypothesizes that genetic variations in CCL2 and its receptor (CCR2) may help explain muscle trait variability. College-aged subjects [n = 874, Functional Single-Nucleotide Polymorphisms Associated With Muscle Size and Strength (FAMUSS) cohort] underwent a 12-wk supervised strength-training program for the upper arm muscles. Muscle size (via MR imaging) and elbow flexion strength (1 repetition maximum and isometric) measurements were taken before and after training. The study participants were then genotyped for 11 genetic variants in CCL2 and five variants in CCR2. Variants in the CCL2 and CCR2 genes show strong associations with several pretraining muscle strength traits, indicating that inflammatory genes in skeletal muscle contribute to the polygenic system that determines muscle phenotypes. These associations extend across both sexes, and several of these genetic variants have been shown to influence gene regulation.
基线肌肉大小和肌肉对运动的适应能力是个体之间高度可变的特征。最近的研究表明，几种趋化因子及其受体参与了许多受炎症过程影响的疾病的发病机制，包括肌肉损伤和修复。一种特定的趋化因子，趋化因子（C-C 基序）配体 2（CCL2），由巨噬细胞和肌肉卫星细胞表达，在肌肉损伤后表达显著增加，并随着反复运动而进一步增加，表明 CCL2 在肌肉适应中发挥关键作用。本研究假设 CCL2 和其受体（CCR2）中的遗传变异可能有助于解释肌肉特征的可变性。大学生受试者[n=874，与肌肉大小和力量相关的功能单核苷酸多态性（FAMUSS）队列]接受了为期 12 周的上肢肌肉监督力量训练计划。在训练前后通过磁共振成像（MR 成像）测量肌肉大小和肘部弯曲强度（1 次重复最大值和等长）。然后，研究参与者对 CCL2 的 11 个遗传变体和 CCR2 的 5 个变体进行了基因分型。CCL2 和 CCR2 基因中的变体与几个训练前肌肉力量特征强烈相关，表明骨骼肌中的炎症基因有助于决定肌肉表型的多基因系统。这些关联跨越了两性，并且已经证明其中的一些遗传变体可以影响基因调控。
