Genetic predictors of long-term response to growth hormone (GH) therapy in children with GH deficiency and Turner syndrome: the influence of a SOCS2 polymorphism
Abstract
BACKGROUND: There is great interindividual variability in the response to GH therapy. Ascertaining genetic factors can improve the accuracy of growth response predictions. Suppressor of cytokine signaling (SOCS)-2 is an intracellular negative regulator of GH receptor (GHR) signaling. OBJECTIVE: The objective of the study was to assess the influence of a SOCS2 polymorphism (rs3782415) and its interactive effect with GHR exon 3 and -202 A/C IGFBP3 (rs2854744) polymorphisms on adult height of patients treated with recombinant human GH (rhGH). DESIGN AND PATIENTS: Genotypes were correlated with adult height data of 65 Turner syndrome (TS) and 47 GH deficiency (GHD) patients treated with rhGH, by multiple linear regressions. Generalized multifactor dimensionality reduction was used to evaluate gene-gene interactions. RESULTS: Baseline clinical data were indistinguishable among patients with different genotypes. Adult height SD scores of patients with at least one SOCS2 single-nucleotide polymorphism rs3782415-C were 0.7 higher than those homozygous for the T allele (P < .001). SOCS2 (P = .003), GHR-exon 3 (P= .016) and -202 A/C IGFBP3 (P = .013) polymorphisms, together with clinical factors accounted for 58% of the variability in adult height and 82% of the total height SD score gain. Patients harboring any two negative genotypes in these three different loci (homozygosity for SOCS2 T allele; the GHR exon 3 full-length allele and/or the -202C-IGFBP3 allele) were more likely to achieve an adult height at the lower quartile (odds ratio of 13.3; 95% confidence interval of 3.2-54.2, P = .0001). CONCLUSION: The SOCS2 polymorphism (rs3782415) has an influence on the adult height of children with TS and GHD after long-term rhGH therapy. Polymorphisms located in GHR, IGFBP3, and SOCS2 loci have an influence on the growth outcomes of TS and GHD patients treated with rhGH. The use of these genetic markers could identify among rhGH-treated patients those who are genetically predisposed to have less favorable outcomes.
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Results from studies of girls with TS are contradictory regarding the effect of d3 alleles on growth response.
“However, the results from studies of girls with TS are contradictory with some finding a significant effect on height velocity, total gain in height and adult height in girls with TS carrying one or two d3 alleles.130-132 Other studies did not find an effect.133-135”
From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [132]
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Clinical practice guidelines for the care of girls and women with Turner syndrome.
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- Authors
- Braz, A. F., Costalonga, E. F., Trarbach, E. B., Scalco, R. C., Malaquias, A. C., Guerra-Junior, G., Antonini, S. R. R., Mendonca, B. B., Arnhold, I. J. P., & Jorge, A. A. L.
- Affiliations
- Universidade de São Paulo (BR)
- Departamento de Pediatria (G.G.-J.), Universidade Estadual de Campinas, 13083–100 Campinas, Brazil
- Corresponding author
- Jorge, Alexander A. L.
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2014-09-01
- Volume
- 99
- Issue
- 9
- Pages
- E1808-E1813
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2112109195
- Cited by
- 30
- References
- 20
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2022: 2 · 2021: 5 · 2020: 3 · 2019: 1 · 2018: 4 · 2017: 1 · 2016: 4 · 2015: 4 · 2014: 1
- FWCI
- 2.68
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Physical Performance
- Keywords
- Turner syndrome, growth hormone deficiency, recombinant human growth hormone therapy, growth hormone receptor, gene-gene interaction, adult height prediction, genetic predictors of treatment response, IGFBP-3
- MeSH terms
- Adolescent, Adult, Child, Female, Genetic Testing, Genotype, Growth Disorders, Humans, Male, Growth Hormone, Turner Syndrome, Treatment Outcome, Human Growth Hormone, Polymorphism, Single Nucleotide, Suppressor of Cytokine Signaling Proteins
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