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The interactive effect of GHR-exon 3 and -202 A/C IGFBP3 polymorphisms on rhGH responsiveness and treatment outcomes in patients with Turner syndrome.

Authors: Braz, Adriana F  Costalonga, Everlayny F  Montenegro, Luciana R  Trarbach, Ericka B  Antonini, Sonir R R  Malaquias, Alexsandra C  Ramos, Ester S  Mendonca, Berenice B  Arnhold, Ivo J P  Jorge, Alexander A L 
Citation: Braz AF, etal., J Clin Endocrinol Metab. 2012 Apr;97(4):E671-7. doi: 10.1210/jc.2011-2521. Epub 2012 Jan 25.
Pubmed: (View Article at PubMed) PMID:22278433
DOI: Full-text: DOI:10.1210/jc.2011-2521


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, R² = 0.27; -202 A/C IGFBP3, R² = 0.24; the combined genotypes, R² = 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.

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RGD Object Information
RGD ID: 12743598
Created: 2017-02-09
Species: All species
Last Modified: 2017-02-09
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.