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, D. Molnár, Luis A. Moreno, Philippe Amouyel, Jean Dallongeville, Aline Meirhaeghe

Research output: Contribution to journalArticle

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Abstract

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 γ 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.

Original languageEnglish
Pages (from-to)5070-5077
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume94
Issue number12
DOIs
Publication statusPublished - Dec 2009

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Angiopoietins
Adiposity
Genetic Polymorphisms
Polymorphism
Lipid Metabolism
Proteins
Gene Frequency
HDL Cholesterol
Adipose Tissue
Fats
Peroxisome Proliferator-Activated Receptors
Waist-Hip Ratio
Apolipoprotein A-I
Plasmas
France
Metabolism
Phenotype
Genes
Tissue
Population

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism

Cite this

Associations between common genetic polymorphisms in angiopoietin-like proteins 3 and 4 and lipid metabolism and adiposity in European adolescents and adults. / Legry, Vanessa; Bokor, Szilvia; Cottel, Dominique; Beghin, Laurent; Catasta, Giovina; Nagy, Eniko; Gonzalez-Gross, Marcela; Spinneker, Andre; Stehle, Peter; Molnár, D.; Moreno, Luis A.; Amouyel, Philippe; Dallongeville, Jean; Meirhaeghe, Aline.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 94, No. 12, 12.2009, p. 5070-5077.

Research output: Contribution to journalArticle

Legry, V, Bokor, S, Cottel, D, Beghin, L, Catasta, G, Nagy, E, Gonzalez-Gross, M, Spinneker, A, Stehle, P, Molnár, D, Moreno, LA, Amouyel, P, Dallongeville, J & Meirhaeghe, A 2009, 'Associations between common genetic polymorphisms in angiopoietin-like proteins 3 and 4 and lipid metabolism and adiposity in European adolescents and adults', Journal of Clinical Endocrinology and Metabolism, vol. 94, no. 12, pp. 5070-5077. https://doi.org/10.1210/jc.2009-0769
Legry, Vanessa ; Bokor, Szilvia ; Cottel, Dominique ; Beghin, Laurent ; Catasta, Giovina ; Nagy, Eniko ; Gonzalez-Gross, Marcela ; Spinneker, Andre ; Stehle, Peter ; Molnár, D. ; Moreno, Luis A. ; Amouyel, Philippe ; Dallongeville, Jean ; Meirhaeghe, Aline. / Associations between common genetic polymorphisms in angiopoietin-like proteins 3 and 4 and lipid metabolism and adiposity in European adolescents and adults. In: Journal of Clinical Endocrinology and Metabolism. 2009 ; Vol. 94, No. 12. pp. 5070-5077.
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abstract = "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 γ 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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T1 - Associations between common genetic polymorphisms in angiopoietin-like proteins 3 and 4 and lipid metabolism and adiposity in European adolescents and adults

AU - Legry, Vanessa

AU - Bokor, Szilvia

AU - Cottel, Dominique

AU - Beghin, Laurent

AU - Catasta, Giovina

AU - Nagy, Eniko

AU - Gonzalez-Gross, Marcela

AU - Spinneker, Andre

AU - Stehle, Peter

AU - Molnár, D.

AU - Moreno, Luis A.

AU - Amouyel, Philippe

AU - Dallongeville, Jean

AU - Meirhaeghe, Aline

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N2 - 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 γ 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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