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
dc.contributor.author BRAZ, Adriana F. FMUSP-HC
COSTALONGA, Everlayny F. FMUSP-HC
MONTENEGRO, Luciana R. FMUSP-HC
TRARBACH, Ericka B. FMUSP-HC
ANTONINI, Sonir R. R.
MALAQUIAS, Alexsandra C. FMUSP-HC
RAMOS, Ester S.
MENDONCA, Berenice B. FMUSP-HC
ARNHOLD, Ivo J. P. FMUSP-HC
JORGE, Alexander A. L. FMUSP-HC
dc.date.issued 2012
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.group LIM/42
dc.description.group LIM/25
dc.description.index MEDLINE
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.identifier.citation JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, v.97, n.4, p.E671-E677, 2012
dc.identifier.doi 10.1210/jc.2011-2521
dc.identifier.issn 0021-972X
dc.identifier.pmid 22278433
dc.identifier.uri http://observatorio.fm.usp.br/handle/OPI/402
dc.language.iso eng
dc.publisher ENDOCRINE SOC
dc.relation.ispartof Journal of Clinical Endocrinology & Metabolism
dc.rights openAccess
dc.rights.holder Copyright ENDOCRINE SOC
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.type.category original article
dc.type.version publishedVersion
hcfmusp.author BRAZ, Adriana F.:FM:
hcfmusp.author COSTALONGA, Everlayny F.:FM:
hcfmusp.author MONTENEGRO, Luciana R.:FM:MCM
hcfmusp.author TRARBACH, Ericka B.:FM:MCM
hcfmusp.author MALAQUIAS, Alexsandra C.:FM:
hcfmusp.author MENDONCA, Berenice B.:FM:MCM
hcfmusp.author ARNHOLD, Ivo J. P.:HC:ICHC
hcfmusp.author JORGE, Alexander A. L.:FM:MCM
hcfmusp.author.external · 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
hcfmusp.origem.id WOS:000302787800024
hcfmusp.publisher.city CHEVY CHASE
hcfmusp.publisher.country USA
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