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.


METHODS
Genotype-phenotype correlation study.


METHODS
University-based pediatric endocrinology practice.


METHODS
Eighty-seven girls with PP and 70 adolescent girls with hyperandrogenism.


METHODS
Blood was obtained for genotype analysis, glucose measurement, and hormone (Delta(4)-A, insulin, 17-hydroxyprogesterone, and T) determinations.


METHODS
Frequency of this SNP in the GAD2 gene and correlation of this SNP with BMI and hormone concentrations.


RESULTS
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.


CONCLUSIONS
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.
Witchel
Selma Feldman
SF
Department of Pediatrics, Division of Endocrinology, Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA. selma.witchel@chp.edu
White
Carlie
C
Libman
Ingrid
I
D015992:Body Mass Index; D002648:Child; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D005968:Glutamate Decarboxylase / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D017588:Hyperandrogenism / Q000235:genetics; D009765:Obesity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011629:Puberty, Precocious / Q000235:genetics*
D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2