Issue |
Med Sci (Paris)
Volume 22, Number 3, Mars 2006
|
|
---|---|---|
Page(s) | 308 - 312 | |
Section | M/S revues | |
DOI | https://doi.org/10.1051/medsci/2006223308 | |
Published online | 15 March 2006 |
ENPP1, premier exemple d’un déterminant génétique commun à l’obésité et au diabète de type 2
ENPP1, the first example of common genetic link between childhood and adult obesity and type 2 diabetes
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
*
philippe.froguel@good.ibl.fr
L’obesite, en particulier ses formes severes, est l’un des principaux facteurs de risque de diabete de type 2. Par ailleurs, l’explosion de l’epidemie d’obesite infantile s’accompagne de l’apparition de formes precoces de diabete de type 2, avec un syndrome metabolique et une intolerance au glucose detectables des l’adolescence. Ces donnees suggerent l’existence de determinants moleculaires primitifs communs entre obesite severe et precoce et diabete de type 2, qui partageraient une insulinoresistance genetiquement determinee. Dans ce contexte, l’identification, sur la region chromosomique 6q liee a la ≪ diabesite ≫, du gene ENPP1 codant pour un inhibiteur du recepteur de l’insuline, dont des variants codants et non codants contribuent au risque genetique de cette affection, est un pas vers la dissection genetique des obesites les plus diabetogenes. Ces resultats ouvrent des perspectives nouvelles vers le profilage genetique et biologique des adolescents obeses, dans une optique de prevention et de traitement de la ≪ diabesite ≫ et de ses complications vasculaires.
Abstract
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.
© 2006 médecine/sciences - Inserm / SRMS
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