European Journal of Applied Physiology

, Volume 113, Issue 8, pp 1997–2004 | Cite as

Genetic polymorphisms associated with exertional rhabdomyolysis

  • Patricia A. DeusterEmail author
  • Carmen L. Contreras-Sesvold
  • Francis G. O’Connor
  • William W. Campbell
  • Kimbra Kenney
  • John F. Capacchione
  • Mark E. Landau
  • Sheila M. Muldoon
  • Elisabeth J. Rushing
  • Yuval Heled
Original Article


Exertional rhabdomyolysis (ER) occurs in young, otherwise healthy, individuals principally during strenuous exercise, athletic, and military training. Although many risk factors have been offered, it is unclear why some individuals develop ER when participating in comparable levels of physical exertion under identical environmental conditions and others do not. This study investigated possible genetic polymorphisms that might help explain ER. DNA samples derived from a laboratory-based study of persons who had never experienced an episode of ER (controls) and clinical ER cases referred for testing over the past several years were analyzed for single nucleotide polymorphisms (SNPs) in candidate genes. These included angiotensin I converting enzyme (ACE), α-actinin-3 (ACTN3), creatine kinase muscle isoform (CKMM), heat shock protein A1B (HSPA1B), interleukin 6 (IL6), myosin light chain kinase (MYLK), adenosine monophosphate deaminase 1 (AMPD1), and sickle cell trait (HbS). Population included 134 controls and 47 ER cases. The majority of ER cases were men (n = 42/47, 89.4 %); the five women with ER were Caucasian. Eighteen African Americans (56.3 %) were ER cases. Three SNPs were associated with ER: CKMM Ncol, ACTN3 R577X, and MYLK C37885A. ER cases were 3.1 times more likely to have the GG genotype of CKMM (odds ratio/OR = 3.1, confidence interval/CI 1.33–7.10), 3.0 times for the XX genotype of ACTN3 SNP (OR = 2.97, CI 1.30–3.37), and 5.7 times for an A allele of MYLK (OR = 21.35, CI 2.60–12.30). All persons with HbS were also ER cases. Three distinct polymorphisms were associated with ER. Further work will be required to replicate these findings and determine the mechanism(s) whereby these variants might confer susceptibility.


α-Actinin 3 Creatine kinase muscle isoform Myosin light chain kinase Sickle cell trait African Americans Exercise injury 



α-Actinin 3


Adenosine monophosphate deaminase 1, isoform M


Angiotensin I converting enzyme


Armed Forces Institute of Pathology


Chi-square test


Creatine kinase muscle isoform


Creatine kinase


Exertional rhabdomyolysis

Type II

Fast twitch (Type II) skeletal muscle fibers


Hardy–Weinberg equilibrium


Heat shock protein A1B


Interleukin 6


Myosin light chain kinase


Myosin’s regulatory light chains


Restriction fragment length polymorphisms


Sickle cell trait


Single nucleotide polymorphisms



The authors acknowledge that this research was funded by grants from the Uniformed Services University (R091CE) and the Comprehensive National Neuroscience Program (G191CR).

Conflict of interest

The views expressed are those of the authors and do not reflect the official position of the Uniformed Services University, Department of the Army, Department of the Air Force, Department of the Navy or the United States Department of Defense. In addition, the authors report no conflict of interest.


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Copyright information

© Springer-Verlag Berlin Heidelberg (Outside the USA) 2013

Authors and Affiliations

  • Patricia A. Deuster
    • 1
    Email author
  • Carmen L. Contreras-Sesvold
    • 1
  • Francis G. O’Connor
    • 1
  • William W. Campbell
    • 2
  • Kimbra Kenney
    • 2
  • John F. Capacchione
    • 3
  • Mark E. Landau
    • 2
  • Sheila M. Muldoon
    • 3
  • Elisabeth J. Rushing
    • 2
  • Yuval Heled
    • 4
  1. 1.Department of Military and Emergency MedicineUniformed Services University of the Health SciencesBethesdaUSA
  2. 2.Department of NeurologyUniformed Services University of the Health SciencesBethesdaUSA
  3. 3.Department of AnesthesiologyUniformed Services University of the Health SciencesBethesdaUSA
  4. 4.Institute of Military Physiology, Heller Institute of Medical ResearchSheba Medical CenterRamat GanIsrael

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