Context: A polymorphism of the growth hormone receptor (GHR) gene resulting in genomic deletion of exon 3 (GHR-d3) has been associated with responsiveness to GH therapy. The data reported so far, however, do vary according to the underlying condition, the replacement dose, and duration of the treatment.

Objective, Design: The aim of this study was to analyze the impact of the GHR genotypes in terms of the initial height velocity (HV) resulting from treatment and the impact upon adult height in patients suffering from severe isolated GH deficiency (IGHD).

Controls, Patients, Setting: A total of 181 subjects (peak stimulated GH 2 ng/mL) were studied. In addition, GHR genotype frequency was compared with an adult healthy control group.

Interventions: Based on the various GHR genotypes, HV, effect of r-hGH dose used and final height were analyzed.

Main Outcome Measures, Results: In the 181 subjects after the first two years on r-hGH treatment, HV-SDS as well as height gain were significantly greater in subjects with the GHR-d3/d3 genotype when compared with the subjects presenting with the GHR-fl/fl genotype (p<0.05). A GHR-d3-allele dose dependent effect was found for both HV-SDS (r: 0.72) and height gain (r: 0.77). However, there was no significant difference in final adult height and height-SDS according to the exon-3 genotypes.

Conclusions: Our results indicate that, in patients with severe IGHD, although the GHR-genotype might play a role in GH responsiveness at least at the beginning of treatment, there is no effect on final height.