Growth Hormone (GH) receptor C.1319 G>T polymorphism, but not exon 3 retention or deletion is associated with better first-year growth response to GH therapy in patients with GH deficiency.

We investigated possible influences of single nucleotide polymorphisms (SNPs) on first-year growth velocity in response to growth hormone (GH) therapy in GH-deficient (GHD) children. We recruited a total of 154 GHD prepubertal children who had undergone GH therapy for 1 y. To exclude the possibility that the genotype/allele variants influenced the height of GHD patients, we studied the same gene polymorphisms in 208 familial short stature (FSS) patients and 100 normal control individuals. In the present study, the first-year growth velocities of GHD patients treated with GH were measured and then compared with the allelic frequencies of various SNP of genes involved in the GH-insulin-like growth factor-I (IGF-I) axis. Only c.1319 G>T of the GH receptor (GHR) gene showed significant correlation with first-year growth velocity (p = 0.02). However, the genetic frequency of the c.1319 G>T polymorphism of GHD did not correlate with FSS and normal controls. Therefore, the c.1319 G>T polymorphism does not influence the height of individuals but can affect the therapeutic efficacy of GH in GHD patients. Moreover, the GHR c.1319 T allele showed higher transcriptional activity and stronger signal transducers and activators of transcription (STAT)-5 Tyr694 phosphorylation. Based on these findings, we conclude that the GHRc.1319 T allele is associated with the therapeutic efficacy of GH replacement therapy.