title: Optimum polygenic profile to resist exertional rhabdomyolysis during a marathon.
abstract: OBJECTIVE
  Exertional rhabdomyolysis can occur in individuals performing various types of exercise but it is unclear why some individuals develop this condition while others do not. Previous investigations have determined the role of several single nucleotide polymorphisms (SNPs) to explain inter-individual variability of serum creatine kinase (CK) concentrations after exertional muscle damage. However, there has been no research about the interrelationship among these SNPs. The purpose of this investigation was to analyze seven SNPs that are candidates for explaining individual variations of CK response after a marathon competition (ACE = 287bp Ins/Del, ACTN3 = p.R577X, CKMM = NcoI, IGF2 = C13790G, IL6 = 174G>C, MLCK = C37885A, TNFα = 308G>A).
  
  
  METHODS
  Using Williams and Folland's model, we determined the total genotype score from the accumulated combination of these seven SNPs for marathoners with a low CK response (n = 36; serum CK <400 U·L-1) vs. marathoners with a high CK response (n = 31; serum CK ≥400 U·L-1).
  
  
  RESULTS
  At the end of the race, low CK responders had lower serum CK (290±65 vs. 733±405 U·L-1; P<0.01) and myoglobin concentrations (443±328 vs. 1009±971 ng·mL-1, P<0.01) than high CK responders. Although the groups were similar in age, anthropometric characteristics, running experience and training habits, total genotype score was higher in low CK responders than in high CK responders (5.2±1.4 vs. 4.4±1.7 point, P = 0.02).
  
  
  CONCLUSIONS
  Marathoners with a lower CK response after the race had a more favorable polygenic profile than runners with high serum CK concentrations. This might suggest a significant role of genetic polymorphisms in the levels of exertional muscle damage and rhabdomyolysis. Yet other SNPs, in addition to exercise training, might also play a role in the values of CK after damaging exercise.
authors.affiliation: Exercise Physiology Laboratory, Camilo José Cela University, Madrid, Spain.
authors.forename: Juan
authors.identifier: http://orcid.org/0000-0002-5785-984X
authors.initials: J
authors.lastname: Del Coso
authors.affiliation: Exercise Physiology Laboratory, Camilo José Cela University, Madrid, Spain.
authors.forename: Marjorie
authors.initials: M
authors.lastname: Valero
authors.affiliation: Exercise Physiology Laboratory, Camilo José Cela University, Madrid, Spain.
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Salinero
authors.affiliation: Exercise Physiology Laboratory, Camilo José Cela University, Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Lara
authors.affiliation: Exercise Physiology Laboratory, Camilo José Cela University, Madrid, Spain.
authors.forename: César
authors.initials: C
authors.lastname: Gallo-Salazar
authors.affiliation: Exercise Physiology Laboratory, Camilo José Cela University, Madrid, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Areces
mesh_terms: D000185:Actinin / Q000097:blood / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D052283:Creatine Kinase, MM Form / Q000097:blood / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009211:Myoglobin / Q000097:blood; D009219:Myosin-Light-Chain Kinase / Q000097:blood / Q000235:genetics; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000235:genetics; D005082:Physical Exertion; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012206:Rhabdomyolysis / Q000097:blood / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D012420:Running; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics
chemical_list: C118456:ACTN3 protein, human; C035170:IGF2 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D009211:Myoglobin; D014409:Tumor Necrosis Factor-alpha; D000185:Actinin; D007335:Insulin-Like Growth Factor II; D009219:Myosin-Light-Chain Kinase; D052283:Creatine Kinase, MM Form; C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A