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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

The-202 A Allele of Insulin-Like Growth Factor Binding Protein-3 (IGFBP3) Promoter Polymorphism Is Associated with Higher IGFBP-3 Serum Levels and Better Growth Response to Growth Hormone Treatment in Patients with Severe Growth Hormone Deficiency

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Author(s):
Costalonga, Everlayny Fiorot [1] ; Antonini, Sonir R. [2] ; Guerra-Junior, Gil [3] ; Mendonca, Berenice Bilharinho [1] ; Arnhold, Ivo J. P. [1] ; Jorge, Alexander A. L. [1]
Total Authors: 6
Affiliation:
[1] Univ Sao Paulo, Fac Med, Lab Hormonios & Genet Mol LIM 42, Unidade Endocrinol Desenvolvimento, BR-05403900 Sao Paulo - Brazil
[2] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Pediat, BR-14049900 Sao Paulo - Brazil
[3] Fac Med Campinas, Dept Pediat, BR-13083100 Sao Paulo - Brazil
Total Affiliations: 3
Document type: Journal article
Source: JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM; v. 94, n. 2, p. 588-595, FEB 2009.
Web of Science Citations: 34
Abstract

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. (J Clin Endocrinol Metab 94: 588-595, 2009) (AU)

FAPESP's process: 05/04726-0 - Molecular characterization of congenital endocrine diseases that affect growth and development
Grantee:Ana Claudia Latronico Xavier
Support type: Research Projects - Thematic Grants