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Is glutamate decarboxylase 2 (GAD2) a genetic link between low birth weight and subsequent development of obesity in children?

Is glutamate decarboxylase 2 (GAD2) a genetic link between low birth weight and subsequent development of obesity in children?

Authors :
David Meyre
Agnès Tounian
Maïté Tauber
Marianne Deweirder
Barbara Heude
Jacques Weill
Patrick Tounian
Philippe Boutin
Béatrice Jouret
Philippe Froguel
Mounir Aout
Génétique des maladies multifactorielles (GMM)
Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS)
Epidémiologie cardiovasculaire et métabolique
Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Recherche en épidémiologie et biostatistique
Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Service d'endocrinologie pédiatrique [CHU Lille]
Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Hôpital Jeanne de Flandre [Lille]
Liquides Ioniques et Interfaces Chargées (LI2C)
Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris)
Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)
Centre de Physiopathologie Toulouse Purpan (CPTP)
Université Toulouse III - Paul Sabatier (UT3)
Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Section of Genomic Medicine
Imperial College London
Genome Centre
Imperial College London-Hammersmith campus
Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)
Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Source :
Journal of Clinical Endocrinology and Metabolism, Journal of Clinical Endocrinology and Metabolism, Endocrine Society, 2005, 90 (4), pp.2384-90. ⟨10.1210/jc.2004-1468⟩, Journal of Clinical Endocrinology and Metabolism, 2005, 90 (4), pp.2384-90. ⟨10.1210/jc.2004-1468⟩
Publication Year :
2005
Publisher :
HAL CCSD, 2005.

Abstract

Low birth weight is a risk factor for obesity and type 2 diabetes. The fetal insulin hypothesis proposes that low birth weight might be mediated partly by genetic factors that impair insulin secretion/sensitivity during the fetal stage, as shown for glucokinase, the ATP-sensitive K+ channel subunit Kir6.2, and the small heterodimer partner genes. Glutamic acid decarboxylase 2 gene (GAD2) overexpression impairs insulin secretion in animals. Recently, polymorphisms in the GAD2 gene were associated with adult morbid obesity. In the present study, we investigated potential effects of the functional -243 A-->G polymorphism in the 5' promoter region of the GAD2 gene on fetal growth, insulin secretion, food intake, and risk of obesity in 635 French Caucasian severely obese children from three different medical centers. The case/control study confirmed the association between the GAD2 single-nucleotide polymorphism (SNP) -243 A-->G and obesity (odds ratio, 1.25; P = 0.04). In addition, SNP -243 GG children carriers showed a 270 g lower birth weight and a 1.5 cm lower birth height compared with AA carriers (P = 0.009 and P = 0.013, respectively). The relation between birth weight and Z score of BMI was linear in AA carrier children (P = 0.00001) and quadratic (U-shaped curve) in AG/GG carrier children (P = 0.0009). G allele children carriers presented a trend toward lower insulinogenic index with 25% reduction of insulin secretion in response to glucose load compared with A carriers (P = 0.09). Eighteen percent of GG obese carriers vs. 5.7% of AA carriers reported binge eating phenotype (P = 0.04). These results confirm the association between GAD2-243 promoter SNP and the risk for obesity and suggest that GAD2 may be a polygenic component of the complex mechanisms linking birth weight to further risk for metabolic diseases, possibly involving the pleiotropic effect of insulin on fetal growth and later on feeding behavior.

Details

Language :
English
ISSN :
0021972X and 19457197
Database :
OpenAIRE
Journal :
Journal of Clinical Endocrinology and Metabolism, Journal of Clinical Endocrinology and Metabolism, Endocrine Society, 2005, 90 (4), pp.2384-90. ⟨10.1210/jc.2004-1468⟩, Journal of Clinical Endocrinology and Metabolism, 2005, 90 (4), pp.2384-90. ⟨10.1210/jc.2004-1468⟩
Accession number :
edsair.doi.dedup.....efc629b5b47110a977bd0f5dfb91c586
Full Text :
https://doi.org/10.1210/jc.2004-1468⟩