CCL2 and CCR2 variants are associated with skeletal muscle strength and change in strength with resistance training.
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.
Department of Integrative Systems Biology, Research Center for Genetic Medicine, Children's National Medical Center, George Washington University, Washington, DC 20010, USA.
Brennan T
BT
Harmon
E Funda
EF
Orkunoglu-Suer
Kasra
K
Adham
Justin S
JS
Larkin
Heather
H
Gordish-Dressman
Priscilla M
PM
Clarkson
Paul D
PD
Thompson
Theodore J
TJ
Angelopoulos
Paul M
PM
Gordon
Niall M
NM
Moyna
Linda S
LS
Pescatello
Paul S
PS
Visich
Robert F
RF
Zoeller
Monica J
MJ
Hubal
Laura L
LL
Tosi
Eric P
EP
Hoffman
Joseph M
JM
Devaney
D000222:Adaptation, Physiological; D000293:Adolescent; D000328:Adult; D001696:Biomechanical Phenomena; D018932:Chemokine CCL2 / Q000235:genetics* / Q000378:metabolism; D016009:Chi-Square Distribution; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007537:Isometric Contraction / Q000235:genetics*; D015810:Linkage Disequilibrium; D008279:Magnetic Resonance Imaging; D008297:Male; D053580:Muscle Strength / Q000235:genetics*; D018482:Muscle, Skeletal / Q000033:anatomy & histology / Q000378:metabolism*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D054390:Receptors, CCR2 / Q000235:genetics* / Q000378:metabolism; D055070:Resistance Training; D013997:Time Factors; D019415:Torque; D014481:United States; D034941:Upper Extremity; D055815:Young Adult
C111835:CCL2 protein, human; C515334:CCR2 protein, human; D018932:Chemokine CCL2; D054390:Receptors, CCR2