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Updated: May 12, 2026
07:59
Functional Characterization of Endogenously Expressed Human RYR1 Variants
Published on: June 9, 2021
Genetic polymorphisms associated with exertional rhabdomyolysis
Patricia A Deuster1, Carmen L Contreras-Sesvold, Francis G O'Connor
1Department of Military and Emergency Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814-4799, USA. patricia.deuster@usuhs.edu
European Journal of Applied Physiology
|April 2, 2013
Summary
Genetic factors may predispose individuals to exertional rhabdomyolysis (ER). Specific gene variations in CKMM, ACTN3, and MYLK were linked to increased ER risk in a study of athletes and military trainees.
Area of Science:
- Exercise Physiology
- Human Genetics
- Molecular Biology
Background:
- Exertional rhabdomyolysis (ER) affects healthy individuals during intense physical activity.
- The underlying reasons for susceptibility to ER remain unclear, despite numerous identified risk factors.
- Investigating genetic predispositions may elucidate why some individuals develop ER under similar exertion conditions.
Purpose of the Study:
- To identify potential genetic polymorphisms associated with the development of exertional rhabdomyolysis (ER).
- To analyze single nucleotide polymorphisms (SNPs) in candidate genes within ER cases and healthy controls.
Main Methods:
- DNA samples from 134 controls and 47 ER cases were analyzed for SNPs in genes including ACE, ACTN3, CKMM, and MYLK.
- Statistical analysis was performed to determine associations between specific genotypes/alleles and ER.
- Sickle cell trait (HbS) presence was also noted and evaluated.
Main Results:
- Three SNPs showed significant association with ER: CKMM Ncol (GG genotype, OR=3.1), ACTN3 R577X (XX genotype, OR=2.97), and MYLK C37885A (A allele, OR=21.35).
- Individuals with the GG genotype of CKMM were 3.1 times more likely to have ER.
- Individuals with the XX genotype of ACTN3 SNP were 3.0 times more likely to have ER.
- Individuals with the A allele of MYLK were 5.7 times more likely to have ER.
- All individuals with sickle cell trait (HbS) were ER cases.
Conclusions:
- Specific genetic polymorphisms in CKMM, ACTN3, and MYLK are associated with an increased risk of exertional rhabdomyolysis.
- Sickle cell trait (HbS) was strongly associated with ER in this cohort.
- Further research is needed to confirm these findings and understand the mechanisms linking these genetic variants to ER susceptibility.
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