CONTEXT: Genetic factors that influence the response to recombinant human GH (rhGH) therapy remain mostly unknown. To date, only the GH receptor gene has been investigated. OBJECTIVE: The aim of the study was to assess the influence of a polymorphism in the IGF-binding protein-3 (IGFBP-3) promoter region (-202 A/C) on circulating IGFBP-3 levels and growth response to rhGH therapy in children with GH deficiency (GHD). DESIGN AND PATIENTS: -202 A/C IGFBP3 genotyping (rs2854744) was correlated with data of 71 children with severe GHD who remained prepubertal during the first year of rhGH treatment. MAIN OUTCOME MEASURES: We measured IGFBP-3 levels and first year growth velocity (GV) during rhGH treatment. RESULTS: Clinical and laboratory data at the start of treatment were indistinguishable among patients with different -202 A/C IGFBP3 genotypes. Despite similar rhGH doses, patients homozygous for the A allele presented higher IGFBP-3 sd score levels and higher mean GV in the first year of rhGH treatment than patients with AC or CC genotypes (first year GV, AA = 13.0 +/- 2.1 cm/yr, AC = 11.4 +/- 2.5 cm/yr, and CC = 10.8 +/- 1.9 cm/yr; P = 0.016). Multiple linear regression analyses demonstrated that the influence of -202 A/C IGFBP3 genotype on IGFBP-3 levels and GV during the first year of rhGH treatment was independent of other variables. CONCLUSION: The -202 A allele of IGFBP3 promoter region is associated with increased IGFBP-3 levels and GV during rhGH treatment in prepubertal GHD children.
CONTEXT: Genetic factors that influence the response to recombinant human GH (rhGH) therapy remain mostly unknown. To date, only the GH receptor gene has been investigated. OBJECTIVE: The aim of the study was to assess the influence of a polymorphism in the IGF-binding protein-3 (IGFBP-3) promoter region (-202 A/C) on circulating IGFBP-3 levels and growth response to rhGH therapy in children with GH deficiency (GHD). DESIGN AND PATIENTS: -202 A/C IGFBP3 genotyping (rs2854744) was correlated with data of 71 children with severe GHD who remained prepubertal during the first year of rhGH treatment. MAIN OUTCOME MEASURES: We measured IGFBP-3 levels and first year growth velocity (GV) during rhGH treatment. RESULTS: Clinical and laboratory data at the start of treatment were indistinguishable among patients with different -202 A/C IGFBP3 genotypes. Despite similar rhGH doses, patients homozygous for the A allele presented higher IGFBP-3 sd score levels and higher mean GV in the first year of rhGH treatment than patients with AC or CC genotypes (first year GV, AA = 13.0 +/- 2.1 cm/yr, AC = 11.4 +/- 2.5 cm/yr, and CC = 10.8 +/- 1.9 cm/yr; P = 0.016). Multiple linear regression analyses demonstrated that the influence of -202 A/C IGFBP3 genotype on IGFBP-3 levels and GV during the first year of rhGH treatment was independent of other variables. CONCLUSION: The -202 A allele of IGFBP3 promoter region is associated with increased IGFBP-3 levels and GV during rhGH treatment in prepubertal GHD children.
Authors: Daniel S Evans; Frederic Cailotto; Neeta Parimi; Ana M Valdes; Martha C Castaño-Betancourt; Youfang Liu; Robert C Kaplan; Martin Bidlingmaier; Ramachandran S Vasan; Alexander Teumer; Gregory J Tranah; Michael C Nevitt; Steven R Cummings; Eric S Orwoll; Elizabeth Barrett-Connor; Jordan B Renner; Joanne M Jordan; Michael Doherty; Sally A Doherty; Andre G Uitterlinden; Joyce B J van Meurs; Tim D Spector; Rik J Lories; Nancy E Lane Journal: Ann Rheum Dis Date: 2014-06-13 Impact factor: 19.103
Authors: Raquel S Jallad; Ericka B Trarbach; Felipe H Duarte; Alexander A L Jorge; Marcello D Bronstein Journal: Pituitary Date: 2015-10 Impact factor: 4.107
Authors: Mariana de Oliveira-Klein; Augusto César Cardoso-Dos-Santos; Alice Tagliani-Ribeiro; Nelson Rosa Fagundes; Ursula Matte; Lavinia Schuler-Faccini Journal: Genet Mol Biol Date: 2018-11-29 Impact factor: 1.771