Glycerophosphocholine Metabolites and Cardiovascular Disease Risk Factors in Adolescents: A Cohort Study

Catriona Syme; Simon Czajkowski; Jean Shin; Michal Abrahamowicz; Gabriel Leonard; Michel Perron; Louis Richer; Suzanne Veillette; Daniel Gaudet; Lisa Strug; Yun Wang; Hongbin Xu; Graeme Taylor; Tomas Paus; Steffany Bennett; Zdenka Pausova

doi:10.1161/CIRCULATIONAHA.116.022993

Glycerophosphocholine Metabolites and Cardiovascular Disease Risk Factors in Adolescents: A Cohort Study

Circulation. 2016 Nov 22;134(21):1629-1636. doi: 10.1161/CIRCULATIONAHA.116.022993. Epub 2016 Oct 18.

Authors

Affiliations

¹ From Hospital for Sick Children, University of Toronto, Canada (C.S., S.C., J.S., L.S., Z.P.); Departments of Physiology and Nutritional Sciences, University of Toronto, Canada (C.S., S.C., J.S., Z.P.); Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada (M.A.); Montreal Neurological Institute, McGill University, Canada (G.L.); Department of Human Sciences, Université du Québec à Chicoutimi, Canada (M.P., S.V.); Department of Health Sciences Université du Québec à Chicoutimi, Canada (L.R.); Community Genomic Centre, Université de Montréal, Chicoutimi, Canada (D.G.); Neural Regeneration Laboratory, Ottawa Institute of Systems Biology, University of Ottawa, Canada (Y.W., H.X., G.T., S.B.); Rotman Research Institute, Baycrest, Toronto, Canada (T.P.); and Departments of Psychology and Psychiatry, University of Toronto, Canada (T.P.).
² From Hospital for Sick Children, University of Toronto, Canada (C.S., S.C., J.S., L.S., Z.P.); Departments of Physiology and Nutritional Sciences, University of Toronto, Canada (C.S., S.C., J.S., Z.P.); Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada (M.A.); Montreal Neurological Institute, McGill University, Canada (G.L.); Department of Human Sciences, Université du Québec à Chicoutimi, Canada (M.P., S.V.); Department of Health Sciences Université du Québec à Chicoutimi, Canada (L.R.); Community Genomic Centre, Université de Montréal, Chicoutimi, Canada (D.G.); Neural Regeneration Laboratory, Ottawa Institute of Systems Biology, University of Ottawa, Canada (Y.W., H.X., G.T., S.B.); Rotman Research Institute, Baycrest, Toronto, Canada (T.P.); and Departments of Psychology and Psychiatry, University of Toronto, Canada (T.P.). zdenka.pausova@sickkids.ca.

PMID: 27756781
DOI: 10.1161/CIRCULATIONAHA.116.022993

Abstract

Background: Glycerophosphocholine (GPC) metabolites modulate atherosclerosis and thus risk for cardiovascular disease (CVD). Preclinical CVD may start during adolescence. Here, we used targeted serum lipidomics to identify a new panel of GPCs, and tested whether any of these GPCs are associated, in adolescence, with classical risk factors of CVD, namely excess visceral fat (VF), elevated blood pressure, insulin resistance, and atherogenic dyslipidemia.

Methods: We studied a population-based sample of 990 adolescents (12-18 years, 48% male), as part of the Saguenay Youth Study. Using liquid chromatography-electrospray ionization-mass spectrometry, we identified 69 serum GPCs within the 450 to 680 m/z range. We measured VF with MRI.

Results: We identified several novel GPCs that were associated with multiple CVD risk factors. Most significantly, PC16:0/2:0 was negatively associated with VF (P=1.4×10^-19), blood pressure (P=7.7×10^-5), and fasting triacylglycerols (P=9.0×10^-5), and PC14:1/0:0 was positively associated with VF (P=3.0×10^-7), fasting insulin (P=5.4×10^-32), and triacylglycerols (P=1.4×10^-29). The Sobel test of mediation revealed that both GPCs mediated their respective relations between VF (as a potential primary exposure) and CVD risk factors (as outcomes, P values<1.3×10^-3). Furthermore, a GPC shown recently to predict incident coronary heart disease in older adults, PC18:2/0:0, was associated with several CVD risk factors in adolescents; these associations were less strong than those with the newly identified GPCs.

Conclusions: We identified novel GPCs strongly associated with multiple CVD risk factors in adolescents. These GPCs may be sensitive indicators of obesity-related risk for CVD outcomes in adults, and may improve biological understanding of CVD risk.

Keywords: adolescent; cardiovascular system; lipid metabolism; metabolomics; obesity.

MeSH terms

Adolescent
Cardiovascular Diseases / blood
Cardiovascular Diseases / etiology*
Child
Cohort Studies
Female
Glycerophosphates / adverse effects*
Humans
Male
Risk Factors

Substances

Glycerophosphates