European Journal of Applied Physiology

, Volume 113, Issue 8, pp 1997–2004

Genetic polymorphisms associated with exertional rhabdomyolysis

  • Patricia A. Deuster
  • 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

DOI: 10.1007/s00421-013-2622-y

Cite this article as:
Deuster, P.A., Contreras-Sesvold, C.L., O’Connor, F.G. et al. Eur J Appl Physiol (2013) 113: 1997. doi:10.1007/s00421-013-2622-y

Abstract

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: CKMMNcol, 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.

Keywords

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

Abbreviations

ACTN3

α-Actinin 3

AMPD1

Adenosine monophosphate deaminase 1, isoform M

ACE

Angiotensin I converting enzyme

AFIP

Armed Forces Institute of Pathology

χ2

Chi-square test

CKMM

Creatine kinase muscle isoform

CK

Creatine kinase

ER

Exertional rhabdomyolysis

Type II

Fast twitch (Type II) skeletal muscle fibers

HWE

Hardy–Weinberg equilibrium

HSPA1B

Heat shock protein A1B

IL6

Interleukin 6

MYLK

Myosin light chain kinase

RLC

Myosin’s regulatory light chains

RFLP

Restriction fragment length polymorphisms

HbS

Sickle cell trait

SNP

Single nucleotide polymorphisms

Copyright information

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

Authors and Affiliations

  • Patricia A. Deuster
    • 1
  • 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