Growth hormone (GH) pharmacogenetics: influence of GH receptor exon 3 retention or deletion on first-year growth response and final height in patients with severe GH deficiency

Autor(es)

Jorge, Alexander A. L. ; Marchisotti, Frederico G. ; Montenegro, Luciana R. ; Carvalho, Luciani R. ; Mendonça, Berenice B. ; Arnhold, Ivo J. P. ^[6]

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM; v. 91, n. 3, p. 1076-1080, Mar. 2006.
• Área do conhecimento: Ciências da Saúde - Medicina
• Assunto(s): Puberdade Hormônio do crescimento humano Bases de dados de ácidos nucleicos

Resumo

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). 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. The study was conducted in the university hospital. Genotype and retrospective analysis was performed on data of 75 children with GHD. Intervention consisted of hGH treatment at a mean dose of 33 µg/kg·d and GHR-exon-3 genotype by multiplex PCR. 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. 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. 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. (AU)

• Processo FAPESP: 02/09687-4 - Estudo in vitro da sensibilidade ao GH de crianças com baixa estatura e investigação dos efeitos dos esteróides sexuais sobre a ação do GH em um modelo celular
• Beneficiário: Alexander Augusto de Lima Jorge
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 00/14092-4 - Diagnóstico molecular das alterações do eixo GHRH-GH-IGF-I
• Beneficiário: Ivo Jorge Prado Arnhold
• Modalidade de apoio: Auxílio à Pesquisa - Temático