[ENPP1, the first example of common genetic link between childhood and adult obesity and type 2 diabetes].
Clinical studies have established the strong link between obesity and type 2 diabetes, especially in children, where the rising prevalence of childhood severe obesity has preceded the recent emergence of early-onset forms of "diabesity". These data suggested a common genetic background shared by both conditions, which was also supported by the identification by genome scans of several diabesity chromosomal regions of linkage. The genetic investigation of early-onset form of familial obesity linkage to chromosome 6q led to the identification of ENPP1, an inhibitor of the insulin receptor, as a possible molecular mechanism behind both obesity and type 2 diabetes. Analysis of the DNA variations of ENPP1 in 6,147 subjects showed association between a combination of variants and both childhood obesity, morbid or moderate obesity in adults and also with type 2 diabetes. This study provides a first molecular basis for the physiopathologic association between severe insulin resistance and obesity, and further type 2 diabetes, and offers a new perspective for prevention and treatment of these conditions.
Meyre
David
D
Laboratoire de Physiologie et de Génomique des Maladies Métaboliques, Unité Mixte de Recherche CNRS 8090, Institut Pasteur de Lille, 1, rue du Professeur Calmette, 59000 Lille, France. meyre@good.ibl.fr
Froguel
Philippe
P
D000328:Adult; D002648:Child; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D018507:Gene Expression Regulation, Developmental; D008040:Genetic Linkage; D014644:Genetic Variation; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D009765:Obesity / Q000150:complications / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D010727:Phosphoric Diester Hydrolases / Q000235:genetics*; D011755:Pyrophosphatases / Q000235:genetics*
D010727:Phosphoric Diester Hydrolases; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1; D011755:Pyrophosphatases