A genome-wide association study reveals variants in ARL15 that influence adiponectin levels.
Détails
Télécharger: BIB_39255DFD99FC.P001.pdf (665.02 [Ko])
Etat: Public
Version: de l'auteur⸱e
Etat: Public
Version: de l'auteur⸱e
ID Serval
serval:BIB_39255DFD99FC
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
A genome-wide association study reveals variants in ARL15 that influence adiponectin levels.
Périodique
PLoS Genetics
Collaborateur⸱rice⸱s
Song Kijoung)
ISSN
1553-7404[electronic]
Statut éditorial
Publié
Date de publication
2009
Volume
5
Numéro
12
Pages
1000768
Langue
anglais
Résumé
The adipocyte-derived protein adiponectin is highly heritable and inversely associated with risk of type 2 diabetes mellitus (T2D) and coronary heart disease (CHD). We meta-analyzed 3 genome-wide association studies for circulating adiponectin levels (n = 8,531) and sought validation of the lead single nucleotide polymorphisms (SNPs) in 5 additional cohorts (n = 6,202). Five SNPs were genome-wide significant in their relationship with adiponectin (P< or =5x10(-8)). We then tested whether these 5 SNPs were associated with risk of T2D and CHD using a Bonferroni-corrected threshold of P< or =0.011 to declare statistical significance for these disease associations. SNPs at the adiponectin-encoding ADIPOQ locus demonstrated the strongest associations with adiponectin levels (P-combined = 9.2x10(-19) for lead SNP, rs266717, n = 14,733). A novel variant in the ARL15 (ADP-ribosylation factor-like 15) gene was associated with lower circulating levels of adiponectin (rs4311394-G, P-combined = 2.9x10(-8), n = 14,733). This same risk allele at ARL15 was also associated with a higher risk of CHD (odds ratio [OR] = 1.12, P = 8.5x10(-6), n = 22,421) more nominally, an increased risk of T2D (OR = 1.11, P = 3.2x10(-3), n = 10,128), and several metabolic traits. Expression studies in humans indicated that ARL15 is well-expressed in skeletal muscle. These findings identify a novel protein, ARL15, which influences circulating adiponectin levels and may impact upon CHD risk.
Mots-clé
Molecular-Weight Adiponectin, Bone-Mineral Density, Small G-Proteins, Insulin-Resistance, Plasma Adiponectin, Metabolic Syndrome, Circulating Adiponectin, Myocardial-Infarction, Serum Concentration, APM1 Gene , Colaus Study
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2010 13:55
Dernière modification de la notice
20/08/2019 14:28