The common exon 3 polymorphism of the growth hormone receptor gene and the effect of growth hormone therapy on growth in Korean patients with Turner syndrome

Abstract

Recombinant human growth hormone (GH) can achieve final adult height gain in girls with Turner syndrome (TS), but its efficacy varies widely across individuals. The exon 3-deleted polymorphism of growth hormone receptor (d3-GHR) has been reported to be associated with responsiveness to GH therapy. The short-term growth response of Turner patients to GH therapy was analysed according to their GHR-exon 3 polymorphism genotype. This was a retrospective study of 175 TS patients. Auxological and endocrine parameters were measured, and the GHR-exon 3 genotype was analysed. Allelic frequencies of GHR-exon 3 genotype were compared between patients with TS and control individuals. GH had been administered to 147 patients, 115 of which remained pre-pubertal after the first follow-up year. Changes in height standard deviation score (SDS), height velocity (HV), body mass index (BMI), IGF-1 and IGF binding protein-3 (IGFBP-3) concentrations were compared between these patients, grouped according to genotype, after the first follow-up year. There was no difference in GHR-exon 3 genotype frequency between the TS and control groups of Koreans. According to the GHR-exon 3 genotype (fl/fl group vs. d3/fl and d3/d3 group), HV gain and height SDS gain did not differ significantly at the first year of GH therapy. Moreover, changes in IGF-1, IGFBP-3 concentration and BMI showed no significant difference between the groups with and without d3-GHR after 1 year of GH therapy. The distribution of the GHR-exon 3 genotype was similar in the TS and control groups in a Korean population. The growth promotion efficacy of GH therapy did not differ significantly between TS patients with and without the d3-GHR allele. These findings indicate that the GHR-exon 3 genotype may not be a major factor to affect the GH response in Korean Turner patients.