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This version published online on November 4, 2009
Journal of Clinical Endocrinology & Metabolism , doi:10.1210/jc.2009-0769
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Submitted on April 14, 2009
Accepted on September 17, 2009

Associations between Common Genetic Polymorphisms in Angiopoietin-Like Proteins 3 and 4 and Lipid Metabolism and Adiposity in European Adolescents and Adults

Vanessa Legry, Szilvia Bokor, Dominique Cottel, Laurent Beghin, Giovina Catasta, Eniko Nagy, Marcela Gonzalez-Gross, Andre Spinneker, Peter Stehle, Dénes Molnár, Luis A. Moreno, Philippe Amouyel, Jean Dallongeville, and Aline Meirhaeghe*

Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 744 (V.L., S.B., D.C., P.A., J.D., A.M.), 59000 Lille, France; Institut Pasteur de Lille (V.L., S.B., D.C., P.A., J.D., A.M.), 59800 Lille, France; University Lille Nord de France (V.L., S.B., D.C., P.A., J.D., A.M.), 59045 Lille, France; Université Droit et Santé de Lille (UDSL) (V.L., S.B., D.C., P.A., J.D., A.M.), 59000 Lille, France; Institut National de Santé et de La Recherche Médicale Unité U995 (L.B.), 59000 Lille, France; Institut de Médecine Prédictive et Thérapeutique, Faculté de Médecine, Université Lille Nord de France (L.B.), 59000 Lille, France; Centre d' Investigation Clinique CIC-9301, Centre Hospitalier & Universitaire de Lille (L.B.), 59000 Lille, France; National Research Institute for Food and Nutrition (G.C.), 00178 Roma, Italy; University of Pécs (E.N., D.M.), Department of Pediatrics, 7624 Pécs, Hungary; Facultad de Ciencias de la Actividad Física y del Deporte-INEF (M.G.-G.), Universidad Politécnica de Madrid, 28040 Madrid, Spain; Institut für Ernährungs-und Lebensmittelwissenschaften–Humanernährung (A.S., P.S.), Rheinische Friedrich-Wilhelms Universität, 53113 Bonn, Germany; and Growth, Exercise, Nutrition and Development Research Group (L.A.M.), Escuela Universitaria de Ciencias de la Salud, Universidad de Zaragoza, 50009 Zaragoza, Spain

* To whom correspondence should be addressed. E-mail: aline.meirhaeghe-hurez{at}pasteur-lille.fr.

Context: Plasma-borne angiopoietin-like proteins (ANGPTL) act as endocrine factors on their target tissues. Because ANGPTL3 and ANGPTL4 play important roles in lipid metabolism and the regulation of adiposity in mice, we hypothesized that genetic variability at the ANGPTL3 and ANGPTL4 genes loci might influence lipid metabolism and fat deposition in humans.

Objective: The aim of the study was to examine the association between ANGPTL3 and ANGPTL4 genetic polymorphisms and metabolic phenotypes in adolescent and adult samples.

Design and Participants: Two independent population-based studies, one composed of 1144 adolescents (mean age, 14.8 ± 1.4 yr) from nine European countries (the HELENA study) and the other composed of 1155 adults (age range, 35–65 yr) from Northern France (the MONICA Lille study), were genotyped for one ANGPTL3 polymorphism and four ANGPTL4 polymorphisms.

Results: The ANGPTL3 rs11207997 polymorphism (minor allele frequency, 0.32) was associated with lower plasma HDL-cholesterol and apolipoprotein A-I levels in both adolescents (P = 0.0004, P = 0.00006, respectively) and adults (P = 0.03, P = 0.02, respectively). The ANGPTL4 rs4076317 polymorphism (minor allele frequency, 0.29) was associated with a higher percentage of body fat (P = 0.02) in adolescents and a higher waist-to-hip ratio (in interaction with the peroxisome proliferator-activated receptor {gamma} Pro12Ala polymorphism) in adults (P = 0.0004).

Conclusion: The present study underlines the role of ANGPTL3 in HDL-cholesterol metabolism as early as in adolescence. Our data also suggest possible associations between ANGPTL4 polymorphisms and body fat, but these findings require replication.






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