Association of the -243 A-->G polymorphism of the glutamate decarboxylase 2 gene with obesity in girls with premature pubarche.
OBJECTIVE: To test the a priori hypothesis that the frequency of a single-nucleotide polymorphism (SNP) located in the promoter region of the glutamate decarboxylase 2 (GAD2) gene (-243A-->G) would be overrepresented among children with higher body mass index (BMI) values. DESIGN: Genotype-phenotype correlation study. SETTING: University-based pediatric endocrinology practice. PATIENT(S): Eighty-seven girls with PP and 70 adolescent girls with hyperandrogenism. INTERVENTION(S): Blood was obtained for genotype analysis, glucose measurement, and hormone (Delta(4)-A, insulin, 17-hydroxyprogesterone, and T) determinations. MAIN OUTCOME MEASURE(S): Frequency of this SNP in the GAD2 gene and correlation of this SNP with BMI and hormone concentrations. RESULT(S): Among the girls followed longitudinally, the presence of one or more G alleles was associated with increased BMI at both initial and recent visits and with greater BMI z score at the initial visit. No associations were found between androgen concentrations and the G-allele variant. CONCLUSION(S): Similar to the findings among French children, this SNP in the GAD2 gene was associated with increased BMI in late childhood and adolescence in this population of girls from western Pennsylvania. Additional prospective studies that replicate our findings are crucial. Verification of our findings will encourage the use of lifestyle interventions for young girls who carry the G allele.[1]References
- Association of the -243 A-->G polymorphism of the glutamate decarboxylase 2 gene with obesity in girls with premature pubarche. Witchel, S.F., White, C., Libman, I. Fertil. Steril. (2009) [Pubmed]
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