CCL2 and CCR2 polymorphisms are associated with markers of exercise-induced skeletal muscle damage
CCL2 and CCR2 polymorphisms are associated with markers of exercise-induced skeletal muscle damage
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DOI：
10.1152/japplphysiol.00361.2009
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发表时间：
2010-06-01
影响因子：
3.3
通讯作者：
Clarkson, Priscilla M.
中科院分区：
文献类型：
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作者：
Hubal, Monica J.;Devaney, Joseph M.;Clarkson, Priscilla M.
Hubal MJ、Devaney JM、Hoffman EP、Zambraski EJ、Gordish-Dressman H、Kearns AK、Larkin JS、Adham K、Patel RR、Clarkson PM。 CCL2 和 CCR2 多态性与运动引起的骨骼肌损伤的标志物相关。 J Appl Physiol 108: 1651-1658, 2010。首次发表于 2010 年 3 月 25 日； doi：10.1152/japplphysicalol。 00361.2009.-新颖的离心（延长收缩）运动通常会导致肌肉损伤，表现为长期肌肉功能障碍、迟发性肌肉酸痛以及肌肉蛋白渗漏到循环中。个体对离心运动的损伤反应存在很大程度的差异，反应较高的人面临潜在致命的横纹肌溶解症的风险。我们假设趋化因子配体 2 (CCL2) 及其受体趋化因子受体 2 (CCR2) 中的单核苷酸多态性 (SNP) 与肌肉损伤反应的高度变异性相关。我们的这一假设基于 CCL2 在受伤肌肉中巨噬细胞和卫星细胞信号传导中的作用。 DNA 是从 157 名未经训练的男性和女性在进行最大离心运动后获得的。测试了单次运动恢复前和恢复期间的力量损失、酸痛、血清肌酸激酶 (CK) 和肌红蛋白水平与 CCL2 和 CCR2 中 16 个 SNP 的关联。 rs768539 和 rs3918358 (CCR2) 的罕见等位基因与男性较低的运动前强度显着相关 (P < 0.05)，而 CCL2 SNP（rs13900、rs1024611 和 rs1860189）和 CCR2 (rs1799865) 与女性运动前 CK 水平的改变相关。在恢复过程中，rs3917878 基因型 (CCL2) 与男性力量恢复减弱和女性 CK 反应升高相关。 CCR2 变异与女性 (rs3918358) 力量恢复较慢以及所有受试者的酸痛程度升高 (rs1799865) 相关。总之，我们发现 CCL2 和 CCR2 中的 SNP 与运动引起的肌肉损伤有关，并且某些变异的存在可能导致对剧烈运动的过度损伤反应。
Hubal MJ, Devaney JM, Hoffman EP, Zambraski EJ, Gordish-Dressman H, Kearns AK, Larkin JS, Adham K, Patel RR, Clarkson PM. CCL2 and CCR2 polymorphisms are associated with markers of exercise-induced skeletal muscle damage. J Appl Physiol 108: 1651-1658, 2010. First published March 25, 2010; doi:10.1152/japplphysiol. 00361.2009.-Novel eccentric (lengthening contraction) exercise typically results in muscle damage, which manifests as prolonged muscle dysfunction, delayed onset muscle soreness, and leakage of muscle proteins into circulation. There is a large degree of variability in the damage response of individuals to eccentric exercise, with higher responders at risk for potentially fatal rhabdomyolysis. We hypothesized that single nucleotide polymorphisms (SNPs) in chemokine ligand 2 (CCL2) and its receptor chemokine receptor 2 (CCR2) associate with the high degrees of variability in the muscle damage response. We based this hypothesis on CCL2' s roles in macrophage and satellite cell signaling in injured muscle. DNA was obtained from 157 untrained men and women following maximal eccentric exercise. Strength loss, soreness, serum creatine kinase (CK), and myoglobin levels before and during recovery from a single exercise bout were tested for association with 16 SNPs in CCL2 and CCR2. The rare alleles for rs768539 and rs3918358 (CCR2) were significantly (P < 0.05) associated with lower preexercise strength in men, whereas CCL2 SNPs (rs13900, rs1024611, and rs1860189) and CCR2 (rs1799865) were associated with altered preexercise CK levels in women. During recovery, the rs3917878 genotype (CCL2) was associated with attenuated strength recovery in men and an elevated CK response in women. CCR2 variants were associated with slower strength recovery in women (rs3918358) and elevated soreness (rs1799865) across all subjects. In summary, we found that SNPs in CCL2 and CCR2 are associated with exercise-induced muscle damage and that the presence of certain variants may result in an exaggerated damage response to strenuous exercise.