title: Genetic polymorphisms associated with exertional rhabdomyolysis.
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.
authors.affiliation: Department 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
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Deuster
authors.forename: Carmen L
authors.initials: CL
authors.lastname: Contreras-Sesvold
authors.forename: Francis G
authors.initials: FG
authors.lastname: O'Connor
authors.forename: William W
authors.initials: WW
authors.lastname: Campbell
authors.forename: Kimbra
authors.initials: K
authors.lastname: Kenney
authors.forename: John F
authors.initials: JF
authors.lastname: Capacchione
authors.forename: Mark E
authors.initials: ME
authors.lastname: Landau
authors.forename: Sheila M
authors.initials: SM
authors.lastname: Muldoon
authors.forename: Elisabeth J
authors.initials: EJ
authors.lastname: Rushing
authors.forename: Yuval
authors.initials: Y
authors.lastname: Heled
mesh_terms: D000659:AMP Deaminase / Q000235:genetics; D000185:Actinin / Q000235:genetics; D000293:Adolescent; D000328:Adult; D001741:Black or African American; D002135:Calcium-Binding Proteins / Q000235:genetics; D016022:Case-Control Studies; D003402:Creatine Kinase / Q000235:genetics; D015444:Exercise; D005260:Female; D056726:Genetic Association Studies; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics; D008297:Male; D009219:Myosin-Light-Chain Kinase / Q000235:genetics; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012206:Rhabdomyolysis / Q000209:etiology / Q000235:genetics*; D012805:Sickle Cell Trait / Q000235:genetics; D044465:White People
chemical_list: C118456:ACTN3 protein, human; D002135:Calcium-Binding Proteins; D018840:HSP70 Heat-Shock Proteins; C525621:HSPA1B protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D000185:Actinin; C499378:MYLK protein, human; D009219:Myosin-Light-Chain Kinase; D003402:Creatine Kinase; C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A; D000659:AMP Deaminase; C514117:AMPD1 protein, human
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