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Sci Rep. 2017 Apr 25;7(1):1130. 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.

Author information

1
Department of Clinical Chemistry, Fimlab Laboratories, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland. ilkka.seppala@uta.fi.
2
Department of Clinical Chemistry, Fimlab Laboratories, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland.
3
Division of Vascular Surgery, Department of Surgery, Tampere University Hospital, Tampere, Finland.
4
Health and Functional Capacity, National Institute for Health and Welfare, Turku, Finland.
5
Computational Medicine, Faculty of Medicine, University of Oulu, Oulu, Finland.
6
NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
7
Department of Paediatrics, University of Tampere and Tampere University Hospital, Tampere, Finland.
8
Institute of Public Health, Social and Preventive Medicine, Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany.
9
Synlab Services GmbH, Mannheim, Germany.
10
Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
11
Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
12
Department of Medicine, Turku University Hospital and University of Turku, Turku, Finland.
13
Department of Clinical Physiology, Tampere University Hospital, and Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland.
14
Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.

Abstract

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.

PMID:
28442717
PMCID:
PMC5430630
DOI:
10.1038/s41598-017-01274-6
[Indexed for MEDLINE]
Free PMC Article

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