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The n-3 long-chain PUFAs modulate the impact of the GCKR Pro446Leu polymorphism on triglycerides in adolescents
Authors:Julien Rousseaux  Alain Duhamel  Julie Dumont  Jean Dallongeville  Denes Molnar  Kurt Widhalm  Yannis Manios  Michael Sj?str?m  Anthony Kafatos  Christina Breidenassel  Marcela Gonzales-Gross  Magdalena Cuenca-Garcia  Laura Censi  Marcos Ascensión  Stefaan De Henauw  Luis A. Moreno  Aline Meirhaeghe  Frédéric Gottrand
Affiliation:2. Unité de Biostatistiques, CERIM, EA2694, CHU Lille, University Lille, Lille, France;3. Inserm UMR1167, Institut Pasteur de Lille, University Lille, Lille, France;4. Department of Pediatrics, University of Pécs, Pécs, Hungary;6. Academic Institute for Clinical Nutrition, Vienna, Austria and Private Medical University Salzburg, Salzburg, Austria;11. Preventive Medicine and Nutrition Unit, School of Medicine, University of Crete, Heraklion, Greece;12. Institut für Ernährungs-und Lebensmittelwissenschaften, Humanernährung, Rheinische Friedrich-Wilhelms, Universität Bonn, Bonn, Germany;8. Facultad de la Actividad Física y del Deporte-INEF, Universidad Politécnica de Madrid, Madrid, Spain;10. Department of Medical Physiology, Faculty of Medicine, Granada University, Granada, Spain;112. Department of Public Health, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium;123. GENUD (Growth, Exercise, Nutrition and Development) Research Group, Escuela Universitaria de Ciencias de la Salud, Universidad de Zaragoza, Zaragoza, Spain
Abstract:Dietary n-3 long-chain PUFAs (LC-PUFAs) are associated with improvement in the parameters of the metabolic syndrome (MetS). Glucokinase regulatory protein (GCKR) is a key protein regulating intracellular glucose disposal. Our aim was to investigate: i) the relationship between the GCKR rs1260326 (Pro446Leu) polymorphism and parameters of the MetS; and ii) a potential influence of n-3 and n-6 LC-PUFA levels on this relationship in the HELENA study (1,155 European adolescents). Linear regression analyses were performed to study the association between rs1260326 and the outcomes of interest. Interactions between rs1260326 and LC-PUFA levels on outcomes were explored. The T allele of rs1260326 was associated with higher serum TG concentrations compared with the C allele. In contrast to n-6 LC-PUFA levels, a significant interaction (P = 0.01) between rs1260326 and total n-3 LC-PUFA levels on serum TG concentrations was observed. After stratification on the n-3 LC-PUFA median values, the association between rs1260326 and TG concentration was significant only in the group with high n-3 LC-PUFA levels. In conclusion, this is the first evidence that n-3 LC-PUFAs may modulate the impact of the GCKR rs1260326 polymorphism on TG concentrations in adolescents. Several molecular mechanisms, in link with glucose uptake, could explain these findings.
Keywords:polyunsaturated fatty acid  glucokinase regulatory protein  lipid metabolism
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