CCL2 and CCR2 polymorphisms are associated with markers of exercise-induced skeletal muscle damage

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.