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

Braz, Adriana Farrant; Costalonga, Everlayny Fiorot; Montenegro, Luciana Ribeiro; Trarbach, Ericka Barbosa; Antonini, Sonir Roberto Rauber; Malaquias, Alexsandra C.; Ramos, Ester Silveira; Mendonca, Berenice B.; Arnhold, Ivo Jorge Prado; Jorge, Alexander A L

doi:10.1210/jc.2011-2521

Cited by 23 publications

(34 citation statements)

References 29 publications

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“…Differences in the number of CA repeats have been associated with serum IGF1 levels, although controversial results have been communicated (3,5,6,7,8). In addition, the number of CA repeats has been associated with various clinical conditions or risk situations, such as age-related IGF1 decline (7), final adult height (4,5,9,10), risk of developing diabetes mellitus and myocardial infarction (5,11), survival after a myocardial infarction in diabetic patients (12), efficacy of recombinant human GH (rhGH) treatment in GH-deficient children, and Turner's syndrome (13,14,15) and cancer susceptibility (16).…”

Section: Introductionmentioning

confidence: 99%

Analysis of IGF(CA)19 and IGFBP3-202A/C gene polymorphisms in patients with acromegaly: association with clinical presentation and response to treatments

Ramos-Leví

Marazuela

Paniagua

et al. 2015

European Journal of Endocrinology

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Objective: IGF1 and IGFBP3 gene polymorphisms have been recently described. However, their potential role in the setting of acromegaly and its outcome is unknown. In this study, we analyze these polymorphisms in patients with acromegaly and investigate their association with clinical presentation and response to treatments. Design: A retrospective observational study was conducted in patients with acromegaly to analyze IGF1 and IGFBP3 gene polymorphisms. Methods: A total of 124 patients with acromegaly (57.3% women, mean age 44.9G13.1 years old) were followed up for a period of 11.4G8.0 years in eight tertiary referral hospitals in Spain. Clinical and analytical data were evaluated at baseline and after treatment. IGF1 and IGFBP3 gene polymorphisms were analyzed using PCR and specific primers. Results: Baseline laboratory test results were GH 19.3 (8.0-39.6) ng/ml, nadir GH 11.8 (4.1-21.5) ng/ml, and index IGF1 2.65G1.25 upper limit of normal. Regarding the IGF1 gene polymorphism, we did not find any association between the number of cyto-adenosine (CA) repeats and patients' baseline characteristics. Nevertheless, a trend for higher nadir GH values was observed in patients with !19 CA repeats. Regarding the IGFBP3 polymorphism, the absence of an A allele at the K202 position was associated with a higher baseline IGF1 and a higher prevalence of cancer and polyps. There were no differences in response to therapies according to the specific genotypes. European Journal of EndocrinologyClinical Study Conclusions: Polymorphisms in the IGF1 and IGFBP3 genes may not be invariably determinant of treatment outcome in acromegalic patients, but they may be associated with higher nadir GH levels or baseline IGF1, and determine a higher rate of colorectal polyps and cancer.

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Section: Introductionmentioning

confidence: 99%

Analysis of IGF(CA)19 and IGFBP3-202A/C gene polymorphisms in patients with acromegaly: association with clinical presentation and response to treatments

Ramos-Leví

Marazuela

Paniagua

et al. 2015

European Journal of Endocrinology

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“…Another hormone receptor, the ERα, also plays a key role in the regulation of linear growth, via stimulation of the pubertal growth spurt and mediation of epiphyseal fusion [30]. The ESR1 rs2234693 polymorphism (PVUII intron 1) has been linked to height during puberty [31, 32] and adulthood [33, 34].…”

Section: Discussionmentioning

confidence: 99%

Genetic Polymorphisms Associated with Idiopathic Short Stature and First-Year Response to Growth Hormone Treatment

Quigley

Brown

et al. 2019

Horm Res Paediatr

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Background/Aims: The term idiopathic short stature (ISS) describes short stature of unknown, but likely polygenic, etiology. This study aimed to identify genetic polymorphisms associated with the ISS phenotype, and with growth response to supplemental GH. Methods: Using a case-control analysis we compared the prevalence of “tall” versus “short” alleles at 52 polymorphic loci (17 in growth-related candidate genes, 35 identified in prior genome-wide association studies of adult height) in 94 children with ISS followed in the Genetics and Neuroendocrinology of Short Stature International Study, versus 143 controls from the Fels Longitudinal Study. Results: Four variants were nominally associated with ISS using a genotypic model, confirmed by a simultaneous confident inference approach: compared with controls children with ISS had lower odds of “tall” alleles (odds ratio, 95% CI) for GHR (0.52, 0.29–0.96); rs2234693/ESR1 (0.50, 0.25–0.98); rs967417/BMP2 (0.39, 0.17–0.93), and rs4743034/ZNF462 (0.40, 0.18–0.89). Children with ISS also had lower odds of the “tall” allele (A) at the IGFBP3 –202 promoter polymorphism (rs2855744; 0.40, 0.20–0.80) in the simultaneous confident inference analysis. A significant association with 1st-year height SD score increase during GH treatment was observed with rs11205277, located near 4 known genes: MTMR11, SV2A, HIST2H2AA3, and SF3B4; the latter, in which heterozygous mutations occur in Nager acrofacial dysostosis, appears the most relevant gene. Conclusions: In children with ISS we identified associations with “short” alleles at a number of height-related loci. In addition, a polymorphic variant located near SF3B4 was associated with the GH treatment response in our cohort. The findings in our small study warrant further investigation.

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“…Ancak bazı araştırıcılar yalnızca klinik değişkenlerin kullanıldığı bu örneklerin yeterli olmadığını ve IGF-1 düzeyleri gibi biyokimyasal değişkenlerin tedaviye yanıtı öngörebilme değerlerini iyileştirebileceğini saptamışlardır (21). Ayrıca BH almacı üzerinde yapılan polimorfizm çalışmaları gelecekte moleküler genetik incelemelerin de öngörü örneklerinde yer alabileceğini düşündürmektedir (7,21).…”

Section: Discussionunclassified

Response to growth hormone therapy in patients with Turner syndrome

Özgen¹,

Adal²,

Ünüvar³

et al. 2013

Turk Pediatri Ars

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ÖzetAmaç: Turner sendromlu hastalarda, boy kısalığı büyüme hormonu ile tedavi edilebilmektedir. Bu çalışmada Turner sendromlu Türk çocuklarında üç yıllık büyüme hormonu tedavisine yanıtı ve tedavi sırasında büyümeye etki edebilecek etmenlerin değerlendirilmesi amaçlanmıştır. Gereç ve Yöntem: Büyüme hormonu tedavisi almış 46 Turner sendromlu hastanın tıbbi kayıtları geriye dönük olarak incelendi. Karyotip, hastaneye başvuru yaşı, büyüme hormonu tedavisi başlama yaşı, anne ve baba boyları, ayrıca tedavinin başlangıcında, birinci, ikinci ve üçüncü yıllarında, çocuğun boy, ağırlık, yıllık büyüme hızı, büyüme hormonu dozu, kemik yaşı ve öngörülen boy değerleri kaydedildi. Hedef boy Z-skoru ve var olan boy Z-skoru arasındaki fark delta Z-skor olarak ifade edildi. Bulgular: Hastaneye başvuru yaşı 10,2±3,8 yıl, tedavi başlangıç yaşı 11,54±3,03 yıl ve hedef boy 157,0±6,0 cm idi. Tedavinin başlangıcında, birinci, ikinci ve üçüncü yılında boy Z-skoru sırasıyla -3,76±1,00, -3,37±1,01, -2,99±0,97, -2,82±1,01 olarak saptandı, yıllık büyüme hızı ise yine sırasıyla 3,24±1,05, 6,53±1,52, 5,77±1,53, 5,19±1,25 cm idi. Birinci yıl büyüme hızı ile tedavi başlangıcındaki kronolojik ve kemik yaşı, delta Z-skor ve baba boyu ile negatif ilişki, büyüme hormonu dozu ile arasında ise pozitif ilişki saptandı. Çoklu regresyon analizlerinde birinci yıl büyüme hızına etki eden en önemli etmenin tedavi başlangıç yaşı ve büyüme hormonu dozu olduğu görüldü. Çıkarımlar: Birinci yıl büyüme hızını etkileyen etmenler; tedavi başlangıç yaşı, büyüme hormonu dozu ve delta Z-skor olarak saptandı. Bu çalışma tanı sonrası çok kısa bir sürede tedavi başlanmasının önemli olduğunu göstermektedir. (Türk Ped Arfl 2013; 48: 294-8) Anahtar sözcükler: Büyüme hormonu, tedavi, Turner sendromu Summary Aim: Short stature, a common feature of Turner syndrome, may be treated effectively by recombinant human growth hormone (rhGH). In this study we aimed to evaluate response to rhGH in the first three years of therapy. Material and Method: Medical records of 46 girls with Turner syndrome treated with rhGH were evaluated retrospectively. Karyotypes, age of admission to the hospital, age of the beginning of rhGH therapy, the height of the mother and father were recorded. Data including, height and weight, growth velocity, dose of rhGH therapy, bone age and predicted height of subjects at the beginning, after first, second and thirds years of rhGH therapy were recorded. Difference between target height Z-score and height Z-score is defined as delta Z-score. Results: Age of admission to hospital, age of beginning of rhGH therapy, target height were 10.2±3.8 years, 11.54±3.03 years and 157.0±6.0 cm respectively. Height Z-score at the beginning, at the end of first, second and thirds year of therapy were -3.76±1.00, -3.37± 1.01, -2.99±0.97, -2.82±1.01 respectively and growth velocity were 3.24±1.05, 6.53±1.52, 5.77±1.53, 5.19±1.25 cm/per year respectively. Bivariate correlation analyzes have revealed that at the first year of therapy growth velocity was correlated negatively w...

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The Interactive Effect ofGHR-Exon 3and −202 A/C IGFBP3Polymorphisms on rhGH Responsiveness and Treatment Outcomes in Patients with Turner Syndrome

Abstract: 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.

Cited by 23 publications

References 29 publications

Analysis of IGF(CA)19 and IGFBP3-202A/C gene polymorphisms in patients with acromegaly: association with clinical presentation and response to treatments

Analysis of IGF(CA)19 and IGFBP3-202A/C gene polymorphisms in patients with acromegaly: association with clinical presentation and response to treatments

Genetic Polymorphisms Associated with Idiopathic Short Stature and First-Year Response to Growth Hormone Treatment

Response to growth hormone therapy in patients with Turner syndrome

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