CKM Glu83Gly Is Associated With Blunted Creatine Kinase Variation, but Not With Myalgia

Abstract

Background-To test the association of a recently reported variant in the creatine kinase (CK) muscle gene, CKM Glu83Gly (rs11559024) with constitutive creatine phosphokinase (CK) levels, CK variation, and inducibility. Given the diagnostic importance of CK in determining muscle damage, we tested the association of the variant with myalgia. ) and 24% (P value=2×10 −5 ) lower for carriers of the variant, respectively. The variant was not associated with myalgia (odds ratio, 0.84; 95% confidence interval, 0.52-1.38).Conclusions-This study highlights that a genetic factor known to be associated with constitutive CK levels is also associated with CK variability and inducibility. This is discussed in the context of evidence to suggest that the variant has an impact on inducibility of CK by trauma through a previously reported case of a homozygous carrier. However, the lack of association between the variant and myalgia suggests that it cannot reliably be used as a biomarker for muscle symptoms.

CKing Precision in the Interpretation of Diagnostic Biomarkers

“…Furthermore, in the current article, Siddiqui et al 11 found that the CKM Glu83Gly variant did not influence the risk of rosuvastatin-induced myalgia in JUPITER, a carefully conducted randomized, placebo-controlled trial. This is consistent with a previous observation that this genetic variant is not associated with statin intolerance.…”

“…Thus, in summary, the study by Siddiqui et al 11 indicates that although the Glu83Gly variant may not be useful in identifying individuals most likely to develop statin-induced muscle complaints, it could perhaps help clinicians to interpret low CK levels in the presence of muscle damage in patients with suspected SAMS or any other diagnosis using CK. As highlighted by the authors, although an allele frequency of 0.02 translates into low carrier prevalence, on a global level, given the growing number on statin users, this could represent a significant number of individuals.…”

“…Given that sex, ethnicity, and recent physical activity have an important impact on CK levels, 9 they should be taken into consideration when interpreting CK levels in the clinic. 3,10 In this issue, Siddiqui et al 11 have further investigated the contribution of CKM Glu83Gly (rs11559024) in explaining the variability in CK levels and whether or not it could help identify patients at a higher risk of statin-induced myalgia. CKM encodes for 1 of the 2 CK dimers, CK-M. 1 The study by Siddiqui et al 11 builds on previous reports from our 12 and other groups 2,13 which have found that genetic variants in the CKM gene influence CK levels.…”

“…3,10 In this issue, Siddiqui et al 11 have further investigated the contribution of CKM Glu83Gly (rs11559024) in explaining the variability in CK levels and whether or not it could help identify patients at a higher risk of statin-induced myalgia. CKM encodes for 1 of the 2 CK dimers, CK-M. 1 The study by Siddiqui et al 11 builds on previous reports from our 12 and other groups 2,13 which have found that genetic variants in the CKM gene influence CK levels. In the current study, the authors have further validated the association between the rs11559024 variant (Glu83Gly) in the CKM gene and baseline CK levels in the GoDARTS (Genetics of Diabetes Audit and Research, Tayside Scotland) and JUPITER (Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin) populations.…”

“…The novelty of the findings presented by Siddiqui et al 11 lies in the longitudinal nature of the GoDARTS study, which has allowed the investigation of intraindividual variability of CK levels by genotype. They found that Gly83 carriers presented a significantly more limited intraindividual variability.…”