Association of the GAA1013→GAG polymorphism of the insulin-like growth factor-1 receptor ( IGF1R) gene with premature pubarche

Abstract

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. Case-control association study. University-based pediatric endocrinology practice. Sixty-nine children (63 girls and 6 boys) with PP, 52 adolescent girls with hyperandrogenism, and 92 healthy subjects. Blood was obtained for genotype analysis, glucose measurement, and hormone (A, insulin, 17-hydroxyprogesterone, and T) determinations. Frequency of the SNP in the IGF1R gene and correlation of this SNP with hormone concentrations. Distribution of the G allele was statistically significantly different between the children with PP and the healthy control subjects, independent of insulin sensitivity. 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.