University of Oulu

Seppälä, I., Oksala, N., Jula, A., Kangas, A., Soininen, P., Hutri-Kähönen, N., März, W., Meinitzer, A., Juonala, M., Kähönen, M., Raitakari, O., Lehtimäki, T. (2017) The biomarker and causal roles of homoarginine in the development of cardiometabolic diseases: an observational and Mendelian randomization analysis. Scientific Reports, 7 (1), doi:10.1038/s41598-017-01274-6

The biomarker and causal roles of homoarginine in the development of cardiometabolic diseases : an observational and Mendelian randomization analysis

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Author: Ilkka Seppälä1; Oksala, Niku1,2; Jula, Antti3;
Organizations: 1Department of Clinical Chemistry, Fimlab Laboratories, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
2Division of Vascular Surgery, Department of Surgery, Tampere University Hospital, Tampere, Finland
3Health and Functional Capacity, National Institute for Health and Welfare, Turku, Finland
4Computational Medicine, Faculty of Medicine, University of Oulu, Oulu, Finland
5NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland
6Department of Paediatrics, University of Tampere and Tampere University Hospital, Tampere, Finland
7Institute of Public Health, Social and Preventive Medicine, Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany
8Synlab Services GmbH, Mannheim, Germany
9Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
10Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland
11Department of Medicine, Turku University Hospital and University of Turku, Turku, Finland
12Department of Clinical Physiology, Tampere University Hospital, and Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
13Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 5.2 MB)
Persistent link:
Language: English
Published: Springer Nature, 2017
Publish Date: 2017-06-28


High L-homoarginine (hArg) levels are directly associated with several risk factors for cardiometabolic diseases whereas low levels predict increased mortality in prospective studies. The biomarker role of hArg in young adults remains unknown. To study the predictive value of hArg in the development of cardiometabolic risk factors and diseases, we utilized data on high-pressure liquid chromatography-measured hArg, cardiovascular risk factors, ultrasound markers of preclinical atherosclerosis and type 2 diabetes from the population-based Young Finns Study involving 2,106 young adults (54.6% females, aged 24–39). We used a Mendelian randomization approach involving tens to hundreds of thousands of individuals to test causal associations. In our 10-year follow-up analysis, hArg served as an independent predictor for future hyperglycaemia (OR 1.31, 95% CI 1.06–1.63) and abdominal obesity (OR 1.60, 95% 1.14–2.30) in men and type 2 diabetes in women (OR 1.55, 95% CI 1.02–2.41). The MR analysis revealed no evidence of causal associations between serum hArg and any of the studied cardiometabolic outcomes. In conclusion, lifetime exposure to higher levels of circulating hArg does not seem to alter cardiometabolic disease risk. Whether hArg could be used as a biomarker for identification of individuals at risk developing cardiometabolic abnormalities merits further investigation.

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Series: Scientific reports
ISSN: 2045-2322
ISSN-E: 2045-2322
ISSN-L: 2045-2322
Volume: 7
Article number: 1130
DOI: 10.1038/s41598-017-01274-6
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
3121 General medicine, internal medicine and other clinical medicine
Funding: The Young Finns Study has been financially supported by the Academy of Finland: grants 286284, 134309 (Eye), 126925, 121584, 124282, 129378 (Salve), 117787 (Gendi), and 41071 (Skidi); the Social Insurance Institution of Finland; Competitive State Research Financing of the Expert Responsibility area of Kuopio, Tampere and Turku University Hospitals (grant X51001); the Juho Vainio Foundation; the Paavo Nurmi Foundation; the Finnish Foundation for Cardiovascular Research; the Finnish Cultural Foundation; the Tampere Tuberculosis Foundation; the Emil Aaltonen Foundation; the Yrjö Jahnsson Foundation; the Signe and Ane Gyllenberg Foundation; and the Diabetes Research Foundation of Finnish Diabetes Association. The quantitative serum NMR metabolomics platform and its development have been supported by the Academy of Finland, TEKES (the Finnish Funding Agency for Technology and Innovation), the Sigrid Juselius Foundation, the Novo Nordisk Foundation, the Finnish Diabetes Research Foundation, the Paavo Nurmi Foundation, and strategic and infrastructural research funding from the University of Oulu, Finland, as well as by the British Heart Foundation, the Wellcome Trust and the Medical Research Council, UK. The expert data management by Irina Lisinen is gratefully acknowledged.
Academy of Finland Grant Number: 286284
Detailed Information: 286284 (Academy of Finland Funding decision)
134309 (Academy of Finland Funding decision)
126925 (Academy of Finland Funding decision)
121584 (Academy of Finland Funding decision)
124282 (Academy of Finland Funding decision)
129378 (Academy of Finland Funding decision)
117787 (Academy of Finland Funding decision)
141071 (Academy of Finland Funding decision)
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