Influence of the Exon 3-Deleted/Full-Length Growth Hormone (GH) Receptor Polymorphism on the Response to GH Replacement Therapy in Adults with Severe GH Deficiency

Context: There is considerable individual variation in the clinical response to GH replacement therapy in GH deficient (GHD) adults. Useful predictors of treatment response are lacking. Objective: The aim of the study was to assess the influence of the exon 3-deleted (d3-GHR) and full-length (fl-GHR) GH-receptor isoforms on the response to GH replacement therapy in adults with severe GHD. Design and Patients: A total of 124 adult GHD patients (79 men; median age, 50 yr) were studied before and after 12 months of GH therapy. GHD patients were divided into those bearing fl/fl alleles (group 1) and those bearing at least one d3-GHR allele (group 2), and the genotype was related to the effects of GH therapy on IGF-I levels and total body fat (BF). Intervention: GH dose was individually titrated to obtain normal serum IGF-I levels. Main Outcome Measures: GHR genotype was determined by PCR amplification, IGF-I levels by immunoassay, and BF by a four-compartment model. Results: Seventy-two (58%) patients had fl/fl genotype and were classified as group 1, whereas 52 (42%) had at least one d3-GHR allele and were classified as group 2 (40 were heterozygous and 12 were homozygous). At baseline, there were no significant differences in the study groups. Changes in IGF-I and BF after 12 months of GH treatment did not differ significantly between the two genotype groups. Conclusion: The presence of d3-GHR allele did not influence the response to GH replacement therapy in our cohort of adults with severe GHD. (J Clin Endocrinol Metab 94: 639-644, 2009)