Associations between common genetic polymorphisms in angiopoietin-like proteins 3 and 4 and lipid metabolism and adiposity in European adolescents and adults.
BACKGROUND
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.


METHODS
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).


CONCLUSIONS
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.
Legry
Vanessa
V
Institut National de la Santé et de la Recherche Médicale Unité 744, Institut Pasteur de Lille, 1 rue du Pr. Calmette, BP 245, F-59019 Lille Cedex, France.
Bokor
Szilvia
S
Cottel
Dominique
D
Beghin
Laurent
L
Catasta
Giovina
G
Nagy
Eniko
E
Gonzalez-Gross
Marcela
M
Spinneker
Andre
A
Stehle
Peter
P
Molnár
Dénes
D
Moreno
Luis A
LA
Amouyel
Philippe
P
Dallongeville
Jean
J
Meirhaeghe
Aline
A
D050154:Adiposity / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000091303:Angiopoietin-Like Protein 3; D000075803:Angiopoietin-Like Protein 4; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins / Q000235:genetics*; D000818:Animals; D000886:Anthropometry; D003430:Cross-Sectional Studies; D005260:Female; D005602:France / Q000453:epidemiology; D005787:Gene Frequency; D014644:Genetic Variation; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics*; D008297:Male; D051379:Mice; D008875:Middle Aged; D009043:Motor Activity; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
C479896:ANGPTL3 protein, human; C474772:ANGPTL4 protein, human; D000091303:Angiopoietin-Like Protein 3; D000075803:Angiopoietin-Like Protein 4; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins