Ckmm Polymorphism Is Associated With The Severity Of Muscle Breakdown Due To Exercise: 564

Exertional Rhabdomyolysis (ER) is a syndrome of skeletal muscle breakdown that results from exercise. In severe cases this syndrome may lead to acute renal failure and even death. Some individuals experience exaggerated changes in their serum creatine kinase (CK) levels, which is the most widely used marker reflective of muscle breakdown. These individuals have been defined as high responders. The reasons for this phenomenon are not fully understood, but a role for genetics has been suggested. PURPOSE: To explore the association between genotypes of the CK muscle gene, CKMM, that serves an important role in skeletal muscle metabolism, and the phenotypic CK response to exercise. METHODS: Healthy, physically active, participants (n = 88) underwent an exercise that included stepping up and down two stairs for 5 min with a backpack, followed by 15 squats. Blood was taken before and after the exercise and 48 and 72 hours after to follow the dynamics of serum CK levels. DNA was extracted from white blood cells for the genetic analysis. RESULTS: Within the sample, 10.2% (9 of 88) were classified as high responders based on their CK responses. Of the 36 participants with the AA genotype, seven (19.4%) were high responders, compared to only two high responders out of the 52 GG and AG genotypes (G+) (3.8%) (p=0.028). Multiple logistic regression analysis of high responders as a function of CKMM genotypes showed that participants with the AA genotype had a 5.7 fold greater risk of being classified as a high responder compared to individuals with a G+ genotype (p<0.05). CONCLUSIONS: The CKMM polymorphism may be important as one of the multifactorial (and probably polygenetic) causes of ER. This finding will require further validation under other exercise paradigms and with a larger sample.