Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Feb 3:7:10572.
doi: 10.1038/ncomms10572.

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

Ragnar P Kristjansson  1 , Asmundur Oddsson  1 , Hannes Helgason  1   2 , Gardar Sveinbjornsson  1 , Gudny A Arnadottir  1 , Brynjar O Jensson  1 , Aslaug Jonasdottir  1 , Adalbjorg Jonasdottir  1 , G Bragi Walters  1 , Gerald Sulem  1 , Arna Oskarsdottir  1 , Stefania Benonisdottir  1 , Olafur B Davidsson  1 , Gisli Masson  1 , Olafur Th Magnusson  1 , Hilma Holm  1   3 , Olof Sigurdardottir  4 , Ingileif Jonsdottir  1 , Gudmundur I Eyjolfsson  5 , Isleifur Olafsson  6 , Daniel F Gudbjartsson  1   2 , Unnur Thorsteinsdottir  1   7 , Patrick Sulem  1 , Kari Stefansson  1   7
Affiliations

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

Ragnar P Kristjansson et al. Nat Commun. .

Abstract

Creatine kinase (CK) and lactate dehydrogenase (LDH) are widely used markers of tissue damage. To search for sequence variants influencing serum levels of CK and LDH, 28.3 million sequence variants identified through whole-genome sequencing of 2,636 Icelanders were imputed into 63,159 and 98,585 people with CK and LDH measurements, respectively. Here we describe 13 variants associating with serum CK and 16 with LDH levels, including four that associate with both. Among those, 15 are non-synonymous variants and 12 have a minor allele frequency below 5%. We report sequence variants in genes encoding the enzymes being measured (CKM and LDHA), as well as in genes linked to muscular (ANO5) and immune/inflammatory function (CD163/CD163L1, CSF1, CFH, HLA-DQB1, LILRB5, NINJ1 and STAB1). A number of the genes are linked to the mononuclear/phagocyte system and clearance of enzymes from the serum. This highlights the variety in the sources of normal diversity in serum levels of enzymes.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Manhattan plot showing the seven loci harbouring genome-wide significant signals influencing serum CK levels in the Icelandic population.
Variants are plotted by chromosomal position (x axis) and −log10 P values (y axis). P values above 1 × 10−25 are represented. Two loci (CKM and LILRB5) harbour variants with P values below this cutoff (rs11559024: P=1.8 × 10−115; rs12975366: P=6.5 × 10−44 and rs393600: P=1.4 × 10−33). The red line indicates the threshold for genome-wide significance, determined by the number of tests performed (P=0.05/28.3 million=1.8 × 10−9).
Figure 2
Figure 2. Manhattan plot showing the 10 loci harbouring genome-wide significant signals influencing serum LDH levels in the Icelandic population.
Variants are plotted by chromosomal position (x axis) and −log10 P values (y axis). P values above 1 × 10−60 are represented. One locus (CD163L1) harbours a variant with P value below this cutoff (rs4072797: P=9.9 × 10−89). The red line indicates the threshold for genome-wide significance, determined by the number of tests performed (P=0.05/28.3 million=1.8 × 10−9).
Figure 3
Figure 3. Locus plots depicting variants at the LILRB5 locus associating with serum enzyme levels.
Leading variants are labelled and shown in purple, other variants are coloured according to correlation (r2) with the leading marker (legend at top-right). −log10 P values are shown along the left y axis and correspond to the variants depicted in the plot. The right y axis shows calculated recombination rates at the chromosomal location, plotted as a solid blue line. (a) Association between the signal represented by rs393600 and serum CK levels. (b) Association between the signal represented by rs12975366 and serum CK levels. (c) Association between the signal represented by rs393600 and serum LDH levels. (d) Association between the signal represented by rs12975366 and serum LDH levels.
See this image and copyright information in PMC

References

    1. Wallimann T., Wyss M., Brdiczka D., Nicolay K. & Eppenberger H. M. Intracellular compartmentation, structure and function of creatine kinase isoenzymes in tissues with high and fluctuating energy demands: the 'phosphocreatine circuit' for cellular energy homeostasis. Biochem. J. 281, 21–40 (1992). - PMC - PubMed
    1. Jacobson T. A. Toward "pain-free" statin prescribing: clinical algorithm for diagnosis and management of myalgia. Mayo Clin. Proc. 83, 687–700 (2008). - PubMed
    1. Jacobson T. A. NLA Task Force on Statin Safety – 2014 update. J. Clin. Lipidol. 8, S1–S4 (2014). - PubMed
    1. Bosch X., Poch E. & Grau J. M. Rhabdomyolysis and acute kidney injury. N. Engl. J. Med. 361, 62–72 (2009). - PubMed
    1. GTEx Portal. Version 4, Build #193. Avaiable at: http://www.gtexportal.org (Accessed on 3 February 2015).

MeSH terms

Substances