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. Design: Case-control association study. Setting: University-based pediatric endocrinology practice. Patient(s): Sixty-nine children (63 girls and 6 boys) with PP, 52 adolescent girls with hyperandrogenism, and 92 healthy subjects. Intervention(s): Blood was obtained for genotype analysis, glucose measurement, and hormone (A, insulin, 17-hydroxyprogesterone, and T) determinations. Main Outcome Measure(s): Frequency of the SNP in the IGFIR gene and correlation of this SNP with hormone concentrations. Result(S): Distribution of the G allele was statistically significantly different between the children with PP and the healthy control subjects, independent of insulin sensitivity. Conclusion(s): This common SNP in the IGFIR 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.