The Interactive Effect of GHR-Exon 3 and -202 A/C IGFBP3 Polymorphisms on rhGH Responsiveness and Treatment Outcomes in Patients with Turner Syndrome

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dc.contributor Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP BRAZ, Adriana F. FMUSP-HC
RAMOS, Ester S.
JORGE, Alexander A. L. FMUSP-HC 2012
dc.identifier.citation JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, v.97, n.4, p.E671-E677, 2012
dc.identifier.issn 0021-972X
dc.description.abstract Context: There is great interindividual variability in the response to recombinant human (rh) GH therapy in patients with Turner syndrome (TS). Ascertaining genetic factors can improve the accuracy of growth response predictions. Objective: The objective of the study was to assess the individual and combined influence of GHR-exon 3 and -202 A/C IGFBP3 polymorphisms on the short-and long-term outcomes of rhGH therapy in patients with TS. Design and Patients: GHR-exon 3 and -202 A/C IGFBP3 genotyping (rs2854744) was correlated with height data of 112 patients with TS who remained prepubertal during the first year of rhGH therapy and 65 patients who reached adult height after 5 +/- 2.5 yr of rhGH treatment. Main Outcome Measures: First-year growth velocity and adult height were measured. Results: Patients carrying at least one GHR-d3 or -202 A-IGFBP3 allele presented higher mean first-year growth velocity and achieved taller adult heights than those homozygous for GHR-fl or -202 C-IGFBP3 alleles, respectively. The combined analysis of GHR-exon 3 and -202 A/C IGFBP3 genotypes showed a clear nonadditive epistatic influence on adult height of patients with TS treated with rhGH (GHR-exon 3 alone, R-2 = 0.27; -202 A/C IGFBP3, R-2 = 0.24; the combined genotypes, R-2 = 0.37 at multiple linear regression). Together with clinical factors, these genotypes accounted for 61% of the variability in adult height of patients with TS after rhGH therapy. Conclusion: Homozygosity for the GHR-exon3 full-length allele and/or the -202C-IGFBP3 allele are associated with less favorable short-and long-term growth outcomes after rhGH treatment in patients with TS.
dc.description.sponsorship · Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [05/04726-0, 05/50144-2]
· Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) [301339/2008-9, 300938/2006-3, 475870/2009-3, 301477/2009-4]
dc.language.iso eng
dc.publisher ENDOCRINE SOC
dc.relation.ispartof Journal of Clinical Endocrinology & Metabolism
dc.rights openAccess
dc.subject.other factor-binding protein-3; growth-hormone treatment; for-gestational-age; receptor polymorphism; promoter polymorphism; serum-levels; gh-receptor; children; height; girls
dc.title The Interactive Effect of GHR-Exon 3 and -202 A/C IGFBP3 Polymorphisms on rhGH Responsiveness and Treatment Outcomes in Patients with Turner Syndrome
dc.type article
dc.rights.holder Copyright ENDOCRINE SOC LIM/42 LIM/25
dc.identifier.doi 10.1210/jc.2011-2521
dc.identifier.pmid 22278433
dc.type.category original article
dc.type.version publishedVersion BRAZ, Adriana F.:FM: COSTALONGA, Everlayny F.:FM: MONTENEGRO, Luciana R.:FM:MCM TRARBACH, Ericka B.:FM:MCM MALAQUIAS, Alexsandra C.:FM: MENDONCA, Berenice B.:FM:MCM ARNHOLD, Ivo J. P.:HC:ICHC JORGE, Alexander A. L.:FM:MCM · ANTONINI, Sonir R. R.:Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Pediat, BR-05508 Sao Paulo, Brazil
· RAMOS, Ester S.:Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Genet, BR-14040900 Sao Paulo, Brazil 2-s2.0-84859527174 WOS:000302787800024 CHEVY CHASE USA
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dc.description.index MEDLINE
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hcfmusp.citation.wos 7

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