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: 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.
Abbreviations
- ACTN3 :
-
α-Actinin 3
- AMPD1 :
-
Adenosine monophosphate deaminase 1, isoform M
- ACE :
-
Angiotensin I converting enzyme
- AFIP:
-
Armed Forces Institute of Pathology
- χ 2 :
-
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
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Acknowledgments
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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Communicated by Martin Flueck.
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Deuster, P.A., Contreras-Sesvold, C.L., O’Connor, F.G. et al. Genetic polymorphisms associated with exertional rhabdomyolysis. Eur J Appl Physiol 113, 1997–2004 (2013). https://doi.org/10.1007/s00421-013-2622-y
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DOI: https://doi.org/10.1007/s00421-013-2622-y