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Unidade de Endocrinologia do Desenvolvimento, Laboratorio de Hormonios e Genetica Molecular LIM/42, Disciplina de Endocrinologia, Hospital das Clinicas, 05403-900, São Paulo, Brazil
Address all correspondence and requests for reprints to: Alexander A. L. Jorge, M.D., Hospital das Clinicas, Laboratorio de Hormonios, Avenida Dr Eneas de Carvalho Aguiar 155 PAMB, 2 andar Bloco 6, 05403-900, São Paulo, Brazil. E-mail: alexj{at}usp.br.
Context: A polymorphism in GHR gene, the presence or absence of exon 3, has been shown to influence the 1- and 2-yr growth responses to human recombinant GH (hGH) therapy in children without GH deficiency (GHD).
Objective: The objective of this study was to assess the influence of GHR-exon-3 genotype on the short and long-term response to hGH therapy in children with GHD.
Setting: The study was conducted in the university hospital.
Design and Patients: Genotype and retrospective analysis was performed on data of 75 children with GHD.
Intervention: Intervention consisted of hGH treatment at a mean dose of 33 µg/kg·d and GHR-exon-3 genotype by multiplex PCR.
Main Outcome Measures: The main outcome measures were GHR genotype: full-length (fl) and exon 3-deleted (d3) alleles, growth velocity in 58 children who remained prepubertal during the first year, and adult height in 44 patients with GHD after 7.5 ± 3.0 yr of treatment.
Results: Clinical and laboratory data at the start of treatment and hGH doses were indistinguishable among patients with different GHR-exon-3 genotypes (fl/fl vs. fl/d3 or d3/d3). Patients carrying at least one GHRd3 allele had a significantly better growth velocity in the first year of hGH replacement (12.3 ± 2.6 vs. 10.6 ± 2.3 cm/yr; P < 0.05) and achieved a taller adult height (final height SD score, –0.8 ± 1.1 vs. –1.7 ± 1.2; P < 0.05) when compared with patients homozygous for GHRfl alleles.
Conclusions: Patients with GHD who are homozygous for GHR exon 3 fl were less responsive to short- and long-term hGH therapy. Approximately half of the population is homozygous for GHRfl, and future studies adjusting hGH therapy to genotype may improve outcome.
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