<i>CKM</i>
            and
            <i>LILRB5</i>
            Are Associated With Serum Levels of Creatine Kinase

Dubé, Marie‐Pierre; Zetler, Rosa Zea; Barhdadi, Amina; Brown, Andrew; Mongrain, Ian; Normand, Valérie; Laplante, Nathalie; Asselin, Géraldine; Zada, Yassamin Feroz; Provost, Sylvie; Bergeron, Jean; Kouz, Simon; Dufour, Robert; Díaz, Ariel; Denus, Simon de; Turgeon, Jacques; Rhéaume, Éric; Phillips, Michael; Tardif, Jean‐Claude

doi:10.1161/circgenetics.113.000395

Cited by 39 publications

(37 citation statements)

References 33 publications

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“…It was suggested to play a role in clearance of creatine kinase via the mononuclear phagocytic system in the liver [78]. LILRB5 is unique among LILRBs in that it is the only LILRB that is not highly expressed by M5 AML cells and in that its expres-sion does not correlate with the overall survival of AML patients based on our analysis of TCGA database of AML patients (https://tcga-data.nci.nih.gov/tcga/).…”

Section: Lilrb5 (Cd85c Lir8)mentioning

confidence: 99%

Inhibitory leukocyte immunoglobulin-like receptors in cancer development

Zhang

Zheng

Kang

et al. 2015

Sci. China Life Sci.

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Inhibitory leukocyte immunoglobulin-like receptors (LILRB1-5) signal through immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in their intracellular domains and recruit phosphatases protein tyrosine phosphatase, non-receptor type 6 (PTPN6, SHP-1), protein tyrosine phosphatase, non-receptor type 6 (PTPN6, SHP-2), or Src homology 2 domain containing inositol phosphatase (SHIP) to negatively regulate immune cell activation. These receptors are known to play important regulatory roles in immune and neuronal functions. Recent studies demonstrated that several of these receptors are expressed by cancer cells. Importantly, they may directly regulate development, drug resistance, and relapse of cancer, and the activity of cancer stem cells. Although counterintuitive, these findings are consistent with the generally immune-suppressive and thus tumor-promoting roles of the inhibitory receptors in the immune system. This review focuses on the ligands, expression pattern, signaling, and function of LILRB family in the context of cancer development. Because inhibition of the signaling of certain LILRBs directly blocks cancer growth and stimulates immunity that may suppress tumorigenesis, but does not disturb normal development, LILRB signaling pathways may represent ideal targets for treating hematological malignancies and perhaps other tumors.

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Section: Lilrb5 (Cd85c Lir8)mentioning

confidence: 99%

Inhibitory leukocyte immunoglobulin-like receptors in cancer development

Zhang

Zheng

Kang

et al. 2015

Sci. China Life Sci.

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“…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.…”

Section: See Article By Siddiqui Et Almentioning

confidence: 84%

CKing Precision in the Interpretation of Diagnostic Biomarkers

Denus

Tardif

Dubé

2017

Circ Cardiovasc Genet

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“…They also report that statin dose and duration of use did not impact this association. 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.…”

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

confidence: 95%

“…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: 95%

“…8,18,19 In addition, CK-M has documented associations with hypothyroidism 20 and blood pressure. 21,22 In 2014, Dubé et al 23 performed an original genome-wide association study in a Canadian population of statin users. They report a single nucleotide polymorphism rs11559024 (Glu83Gly) in CKM as being associated with serum CK levels.…”

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

confidence: 99%

See 1 more Smart Citation

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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CKM and LILRB5 Are Associated With Serum Levels of Creatine Kinase

Abstract: This is the first genome-wide study to report on the underlying genetic determinants of CK variation in a population of statin users. We found statistically significant association for variants in the CKM and LILRB5 genes.

Cited by 39 publications

References 33 publications

Inhibitory leukocyte immunoglobulin-like receptors in cancer development

Inhibitory leukocyte immunoglobulin-like receptors in cancer development

CKing Precision in the Interpretation of Diagnostic Biomarkers

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

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