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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

Department of Endocrinology (E.J.L.B., J.P., C.A.M.G., H.F., J.K., B-Å.B., G.J.), the Sahlgrenska Academy, Sahlgrenska University Hospital, SE-41345 Göteborg, Sweden; SEMPR (E.J.L.B., C.L.B.), Serviço de Endocrinologia e Metabologia do Hospital de Clínicas da Universidade Federal do Paraná, 80030-110 Curitiba, Brazil; and Department of Molecular and Clinical Medicine (L.M.S.C), Institute of Medicine, the Sahlgrenska Academy, Göteborg University, SE-41345 Göteborg, Sweden

Address all correspondence and requests for reprints to: Edna J. L. Barbosa, M.D., Sahlgrenska University Hospital, Institution of Internal Medicine, Department of Endocrinology, Gröna Straket 8, SE-41345 Göteborg, Sweden. E-mail: edna.barbosa{at}medic.gu.se.

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.