Variants of ENPP1 are associated with childhood and adult obesity and increase the risk of glucose intolerance and type 2 diabetes - IFR69 Accéder directement au contenu
Article Dans Une Revue Nature Genetics Année : 2005

Variants of ENPP1 are associated with childhood and adult obesity and increase the risk of glucose intolerance and type 2 diabetes

David Meyre
Nabila Bouatia-Naji
Christian Dina

Résumé

We identified a locus on chromosome 6q16.3-q24.2 (ref. 1) associated with childhood obesity that includes 2.4 Mb common to eight genome scans for type 2 diabetes (T2D) or obesity. Analysis of the gene ENPP1 (also called PC-1), a candidate for insulin resistance, in 6,147 subjects showed association between a three-allele risk haplotype (K121Q, IVS20delT-11 and A-->G+1044TGA; QdelTG) and childhood obesity (odds ratio (OR) = 1.69, P = 0.0006), morbid or moderate obesity in adults (OR = 1.50, P = 0.006 or OR = 1.37, P = 0.02, respectively) and T2D (OR = 1.56, P = 0.00002). The Genotype IBD Sharing Test suggested that this obesity-associated ENPP1 risk haplotype contributes to the observed chromosome 6q linkage with childhood obesity. The haplotype confers a higher risk of glucose intolerance and T2D to obese children and their parents and associates with increased serum levels of soluble ENPP1 protein in children. Expression of a long ENPP1 mRNA isoform, which includes the obesity-associated A-->G+1044TGA SNP, was specific for pancreatic islet beta cells, adipocytes and liver. These findings suggest that several variants of ENPP1 have a primary role in mediating insulin resistance and in the development of both obesity and T2D, suggesting that an underlying molecular mechanism is common to both conditions.
Fichier principal
Vignette du fichier
nihms4824.pdf (694.47 Ko) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)

Dates et versions

hal-00174474 , version 1 (25-01-2022)

Identifiants

Citer

David Meyre, Nabila Bouatia-Naji, Agnès Tounian, Chantal Samson, Cécile Lecoeur, et al.. Variants of ENPP1 are associated with childhood and adult obesity and increase the risk of glucose intolerance and type 2 diabetes. Nature Genetics, 2005, 37 (8), pp.863-7. ⟨10.1038/ng1604⟩. ⟨hal-00174474⟩
378 Consultations
24 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More