Catriona Syme1, Simon Czajkowski1, Jean Shin1, Michal Abrahamowicz1, Gabriel Leonard1, Michel Perron1, Louis Richer1, Suzanne Veillette1, Daniel Gaudet1, Lisa Strug1, Yun Wang1, Hongbin Xu1, Graeme Taylor1, Tomas Paus1, Steffany Bennett1, Zdenka Pausova2. 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.
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.
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.
Authors: Keith Unger; Yaoxiang Li; Celine Yeh; Ana Barac; Monvadi B Srichai; Elizabeth A Ballew; Michael Girgis; Meth Jayatilake; Vijayalakshmi Sridharan; Marjan Boerma; Amrita K Cheema Journal: Radiother Oncol Date: 2020-04-20 Impact factor: 6.280
Authors: Sven W Meckelmann; Jade I Hawksworth; Daniel White; Robert Andrews; Patricia Rodrigues; Anne O'Connor; Jorge Alvarez-Jarreta; Victoria J Tyrrell; Christine Hinz; You Zhou; Julie Williams; Maceler Aldrovandi; William J Watkins; Adam J Engler; Valentina Lo Sardo; David A Slatter; Stuart M Allen; Jay Acharya; Jacquie Mitchell; Jackie Cooper; Junken Aoki; Kuniyuki Kano; Steve E Humphries; Valerie B O'Donnell Journal: Circ Genom Precis Med Date: 2020-05-12