Siddiqui Moneeza Kalhan, Veluchamy Abirami, Maroteau Cyrielle, Tavendale Roger, Carr Fiona, Pearson Ewan, Colhoun Helen, Morris Andrew D, George Jacob, Doney Alexander, Pirmohamed Munir, Alfirevic Ana, Wadelius Mia, Maitland van der Zee Anke H, Ridker Paul M, Chasman Daniel I, Palmer Colin N A
From the Pat McPherson Centre for Pharmacogenetics and Pharmacogenomics, Division of Molecular and Clinical Medicine, Ninewells Hospital and Medical School, University of Dundee, United Kingdom (M.K.S., A.V., C.M., R.T., F.C., E.P., J.G., A.D., C.N.A.P.); Centre for Genomic and Experimental Medicine (H.C.) and Usher Institute of Population Health Sciences and Informatics (A.D.M.), University of Edinburgh, United Kingdom; Institute of Translational Medicine, University of Liverpool, United Kingdom (M.P., A.A.); Department of Medical Sciences, Clinical Pharmacology and Science of Life Laboratory, Uppsala University, Sweden (M.W.); Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, The Netherlands (A.H.M.v.d.Z.); Department of Respiratory Medicine, Academic Medical Center, University of Amsterdam, The Netherlands (A.H.M.v.d.Z.); Brigham and Women's Hospital and Harvard Medical School, Boston, MA (P.M.R., D.I.C.).
Circ Cardiovasc Genet. 2017 Aug;10(4). doi: 10.1161/CIRCGENETICS.117.001737.
To test the association of a recently reported variant in the creatine kinase (CK) muscle gene, 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.
Meta-analysis between longitudinal cohort GoDARTS (Genetics of Diabetes Audit and Research, Tayside Scotland), minor allele frequency (=0.02), and randomized clinical trial (JUPITER [Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin], minor allele frequency=0.018) was used to replicate the association with baseline CK measures. GoDARTS was used to study the relationship with CK variability. Myalgia was studied in JUPITER trial participants. Baseline and SDs of CK were on average 18% ( value=6×10) and 24% ( value=2×10) 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).
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.
为了测试肌酸激酶（CK）肌肉基因中最近报道的一个变体Glu83Gly（rs11559024）与组成型肌酸磷酸激酶（CK）水平、CK变化及诱导性之间的关联。鉴于CK在确定肌肉损伤方面的诊断重要性，我们测试了该变体与肌痛之间的关联。
采用纵向队列GoDARTS（苏格兰泰赛德糖尿病审计与研究遗传学）（次要等位基因频率=0.02）和随机临床试验（JUPITER [瑞舒伐他汀在一级预防中的应用：一项评估瑞舒伐他汀的干预试验]，次要等位基因频率=0.018）之间的荟萃分析来重复该变体与基线CK测量值之间的关联。利用GoDARTS研究该变体与CK变异性之间的关系。在JUPITER试验参与者中研究肌痛情况。该变体携带者的CK基线值和标准差平均分别低18%（P值=6×10⁻⁴）和24%（P值=2×10⁻³）。该变体与肌痛无关（优势比，0.84；95%置信区间，0.52 - 1.38）。
本研究强调，一个已知与组成型CK水平相关的遗传因素也与CK变异性和诱导性相关。结合证据讨论了这一情况，证据表明该变体通过先前报道的一名纯合子携带者的病例对创伤引起的CK诱导性有影响。然而，该变体与肌痛之间缺乏关联表明它不能可靠地用作肌肉症状的生物标志物。
