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Submitted on September 7, 2005
Accepted on November 9, 2005
Unidade de Endocrinologia do Desenvolvimento, Laboratorio de Hormonios e Genetica Molecular LIM/42, Disciplina de Endocrinologia, Hospital das Clinicas, Sao Paulo, Brazil
* To whom correspondence should be addressed. 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 one and two-year growth responses to hGH therapy in children without GH deficiency (GHD).
Objective: Assess the influence of GHR-exon-3 genotype on the short and long-term response to hGH therapy in children with GHD.
Setting: University hospital.
Design and Patients: Genotype and retrospective analysis of data of 75 children with GHD.
Intervention: hGH treatment at mean dose of 33 µg/kg/d. GHR-exon-3 genotype by multiplex PCR.
Main outcome measures: GHR genotype: full-length (fl) and exon 3 deleted (d3) alleles. Growth velocity (GV) 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 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 GV in the first year of hGH replacement (12.3 ± 2.6 vs. 10.6 ± 2.3 cm/year, P < 0.05) and achieved a taller adult height (final height SDS -0.8 ± 1.1 vs. -1.7 ± 1.2, P < 0.05) when compared with patients homozygous for GHRfl alleles.
Conclusions: Patients with growth hormone deficiency who are homozygous for GHR exon 3 full-length 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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