ENPP1, the first example of common genetic link between childhood and adult obesity and type 2 diabetes

Médecine sciences : M/S
D Meyre, P Froguel

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.

References

Apr 16, 1998·International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity·J HagerP Froguel
Jul 21, 2000·The Journal of Clinical Investigation·C VaisseP Froguel
Sep 21, 2002·Lancet·Cara B EbbelingDavid S Ludwig
Oct 2, 2002·American Journal of Human Genetics·Larry D AtwoodRalph B D'Agostino
Dec 31, 2002·JAMA : the Journal of the American Medical Association·Ali H MokdadJames S Marks
Dec 13, 2003·The Journal of Clinical Endocrinology and Metabolism·Nicola AbateScott M Grundy
Dec 24, 2003·PLoS Biology·Philippe BoutinPhilippe Froguel
May 25, 2004·Archives of Disease in Childhood·J WeillP Froguel

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Citations

Jul 11, 2007·International Journal of Obesity : Journal of the International Association for the Study of Obesity·F DaiS T McGarvey

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