Association of the GAA1013-->GAG polymorphism of the insulin-like growth factor-1 receptor (IGF1R) gene with premature pubarche.
OBJECTIVE
A single-nucleotide polymorphism (SNP), the G variant in codon 1013 (GAA1013-->GAG) of the insulin-like growth factor-1 (IGF-1) receptor (IGFIR) gene, has been associated with higher IGF-1 concentrations in Caucasian subjects. Because elevated serum levels of IGF-1 have been described in children with premature pubarche (PP) and in adolescent girls with hyperandrogenism, we tested the a priori hypothesis that the frequency of the A-->G variant would be overrepresented among children with PP.


METHODS
Case-control association study.


METHODS
University-based pediatric endocrinology practice.


METHODS
Sixty-nine children (63 girls and 6 boys) with PP, 52 adolescent girls with hyperandrogenism, and 92 healthy subjects.


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


METHODS
Frequency of the SNP in the IGF1R gene and correlation of this SNP with hormone concentrations.


RESULTS
Distribution of the G allele was statistically significantly different between the children with PP and the healthy control subjects, independent of insulin sensitivity.


CONCLUSIONS
This common SNP in the IGF1R gene may be associated with PP caused by premature adrenarche in children. Because PP has been associated with higher IGF-1 concentrations, these data suggest a potential molecular basis for prior clinical observations of elevated IGF-1 concentrations in children with PP.
Roldan
Maria Belen
MB
Division of Endocrinology, Department of Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
White
Carlie
C
Witchel
Selma Feldman
SF
D000293:Adolescent; D015992:Body Mass Index; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D008040:Genetic Linkage; D005838:Genotype; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D008137:Longitudinal Studies; D008297:Male; D011110:Polymorphism, Genetic; D011629:Puberty, Precocious / Q000235:genetics*; D017526:Receptor, IGF Type 1 / Q000235:genetics*; D013255:Steroid 21-Hydroxylase / Q000235:genetics
D013255:Steroid 21-Hydroxylase; D017526:Receptor, IGF Type 1