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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?
- 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.
- Subjects :
- Male
MESH: Introns
Endocrinology, Diabetes and Metabolism
medicine.medical_treatment
Clinical Biochemistry
Glutamate decarboxylase
Type 2 diabetes
MESH: Base Sequence
Biochemistry
Body Mass Index
MESH: Variation (Genetics)
MESH: Genotype
0302 clinical medicine
Endocrinology
MESH: Child
Insulin Secretion
Birth Weight
Insulin
MESH: Obesity
Child
2. Zero hunger
0303 health sciences
Glutamate Decarboxylase
MESH: Polymorphism, Single Nucleotide
MESH: Infant, Newborn
MESH: Reference Values
MESH: Adiponectin
MESH: Promoter Regions (Genetics)
MESH: Insulin Resistance
MESH: Feeding Behavior
Female
medicine.symptom
MESH: Glutamate Decarboxylase
medicine.medical_specialty
MESH: Mutation
MESH: Diabetes Mellitus
Adolescent
Birth weight
030209 endocrinology & metabolism
MESH: Infant, Low Birth Weight
MESH: Insulin
Biology
Polymorphism, Single Nucleotide
GAD2
MESH: Body Mass Index
03 medical and health sciences
Internal medicine
MESH: Body Height
medicine
Humans
Obesity
MESH: Birth Weight
MESH: Intercellular Signaling Peptides and Proteins
030304 developmental biology
MESH: Adolescent
MESH: Humans
Glucokinase
MESH: Antigens, CD36
Biochemistry (medical)
Infant, Newborn
Feeding Behavior
Infant, Low Birth Weight
medicine.disease
Body Height
MESH: Male
MESH: France
Low birth weight
[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics
MESH: Exons
MESH: Female
Subjects
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⟩