Common and rare variants associating with serum levels of creatine kinase and lactate dehydrogenase

Kristjansson, Ragnar P.; Oddsson, Ásmundur; Helgason, Hannes; Sveinbjörnsson, Garðar; Arnadottir, Gudny A.; Jensson, Brynjar O.; Jónasdóttir, Áslaug; Jónasdóttir, Aðalbjörg; Walters, G. Bragi; Sulem, Gerald; Óskarsdóttir, Arna; Benónísdóttir, Stefania; Davidsson, Olafur B.; Másson, Gísli; Magnússon, Ólafur Þ.; Hólm, Hilma; Sigurðardóttir, Ólöf; Jónsdóttir, Ingileif; Eyjolfsson, Gudmundur I.; Ólafsson, Ísleifur; Guðbjartsson, Daníel F.; Þorsteinsdóttir, Unnur; Sulem, Patrick; Stefánsson, Kāri

doi:10.1038/ncomms10572

Cited by 66 publications

(56 citation statements)

References 57 publications

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“…In an Icelandic cohort of 63 159 individuals, the reported allele frequency was 0.0215. 2 Consistent with previous reports, 2,12 Siddiqui et al 11 found that the association between CKM Glu83Gly and CK levels is independent of statin use.…”

Section: See Article By Siddiqui Et Alsupporting

confidence: 87%

“…This is consistent with a previous observation that this genetic variant is not associated with statin intolerance. 2 Nevertheless, it is important to highlight that in JUPITER, as in most randomized controlled double-blind trials and observational studies, 5,15 no dedicated questionnaire to query patients systematically about muscle complaints was used. Alas, it has become apparent during recent years that the difficulty in identifying genetic risk factors of statin-induced myalgia may lie in the lack of precision in defining it compared with more severe manifestations, such as rhabdomyolysis.…”

Section: De Denus Et Al Ck and Precision Medicinementioning

confidence: 99%

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CKing Precision in the Interpretation of Diagnostic Biomarkers

Denus

Tardif

Dubé

2017

Circ Cardiovasc Genet

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Section: See Article By Siddiqui Et Alsupporting

confidence: 87%

Section: De Denus Et Al Ck and Precision Medicinementioning

confidence: 99%

CKing Precision in the Interpretation of Diagnostic Biomarkers

Denus

Tardif

Dubé

2017

Circ Cardiovasc Genet

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“…23 The minor allele frequency (MAF) in the Canadian study was 0.010. 23 Kristjansson et al 4 replicated these findings in a genome-wide association study performed on 63 159 Icelanders with CK measurements. They report the main effect of the CKM Glu83Gly variant as being associated with serum CK (β=−0.446, P value=1.8×10 −115 ).…”

Section: See Editorial By De Denus Et Al See Clinical Perspectivementioning

confidence: 80%

“…The MAF in the Icelandic cohort was 0.0215. 4 Given the robust association and biologically apparent role of the gene in the production of CK, we wanted to gain insight into the relationship between the variant and CK response. Because CK elevations in response to appropriate stressors is the clinically significant feature of the biomarker, we sought to understand the impact of the variant on inducibility of CK.…”

Section: See Editorial By De Denus Et Al See Clinical Perspectivementioning

confidence: 99%

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

Siddiqui

Veluchamy

Maroteau

et al. 2017

Circ Cardiovasc Genet

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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.

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“…Myocardial enzymes, CK and LDH, are commonly used markers of myocardial injury (Kristjansson et al, 2016). To evaluate the degree of myocardial injury, the activities of CK and LDH were detected using commercial kits.…”

Section: Discussionmentioning

confidence: 99%

Penehyclidine hydrochloride protects against anoxia/reoxygenation injury in cardiomyocytes through ATP‐sensitive potassium channels, and the Akt/GSK‐3β and Akt/mTOR signaling pathways

Zhang

Yang

et al. 2020

Cell Biology International

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Penehyclidine hydrochloride (PHC) can protect against myocardial ischemia/reperfusion (I/R) injury. However, the possible mechanisms of PHC in anoxia/reoxygenation (A/R)-induced injury in H9c2 cells remain unclear. In the present study, H9c2 cells were pretreated with PI3K/Akt inhibitor LY294002, ATP-sensitive K + (KATP) channel blocker 5-hydroxydecanoate (5-HD), PHC, or KATP channel opener diazoxide (DZ) before subjecting to A/R injury. Cell viability and cell apoptosis were determined by cell counting kit-8 assay and annexin V/PI assay, respectively. Myocardial injury was evaluated by measuring creatine kinase (CK) and lactate dehydrogenase (LDH) activities. Intracellular Ca 2+ levels, reactive oxygen species (ROS) generation, mitochondrial membrane potential (ΔΨ m ), and mitochondrial permeability transition pore (mPTP) were measured. The levels of cytoplasmic/mitochondrial cytochrome c (Cyt-C), Bax, Bcl-2, cleaved caspase-3, KATP channel subunits (Kir6.2 and SUR2A), and the members of the Akt/GSK-3β and Akt/mTOR signaling pathways were determined by western blotting. We found that PHC preconditioning alleviated A/R-induced cell injury by increasing cell viability, reducing CK and LDH activities, and inhibiting cell apoptosis. In addition, PHC preconditioning ameliorated intracellular Ca 2+ overload and ROS production, accompanied by inhibition of both mPTP opening and Cyt-C release into cytoplasm, and maintenance of ΔΨ m . Moreover, PHC preconditioning activated mitochondrial KATP channels, and modulated the Akt/GSK-3β and Akt/mTOR signaling pathways. Similar effects were observed upon treatment with DZ. Pretreatment with LY294002 or 5-HD blocked the beneficial effects of PHC. These results suggest that the protective effects of PHC preconditioning on A/R injury may be related to mitochondrial KATP channels, as well as the Akt/GSK-3β and Akt/mTOR signaling pathways.

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Common and rare variants associating with serum levels of creatine kinase and lactate dehydrogenase

Cited by 66 publications

References 57 publications

CKing Precision in the Interpretation of Diagnostic Biomarkers

CKing Precision in the Interpretation of Diagnostic Biomarkers

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

Penehyclidine hydrochloride protects against anoxia/reoxygenation injury in cardiomyocytes through ATP‐sensitive potassium channels, and the Akt/GSK‐3β and Akt/mTOR signaling pathways

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