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  • Title: 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.
    Author: Barbosa EJ, Palming J, Glad CA, Filipsson H, Koranyi J, Bengtsson BA, Carlsson LM, Boguszewski CL, Johannsson G.
    Journal: J Clin Endocrinol Metab; 2009 Feb; 94(2):639-44. PubMed ID: 19050057.
    Abstract:
    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.
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