GHR and VDR Genes do not Contribute to the Growth Hormone (GH) Response in GH Deficient and Turner Syndrome Patients

Álvarez-Nava, Francisco; Marcano, Héctor; Pardo, Tatiana; Paoli, Mariela; Günczler, Peter; Soto, Marisol; Villaloboss, Joalice; Lanes, Roberto

doi:10.1515/jpem.2010.127

Cited by 10 publications

(27 citation statements)

References 24 publications

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“…To analyze the growth response to rhGH, anthropometric data were evaluated at the start of rhGH therapy and every 3 months thereafter for 2 years . Growth velocities, total height gain and differences in the increment were calculated [4]. Recombinant human growth hormone (rhGH) was administered at a mean dose of 37 ± 5 μg/kg/day seven days a week by subcutaneous injection for a two year period.…”

Section: Methodsmentioning

confidence: 99%

Effect of the parental origin of the X-chromosome on the clinical features, associated complications, the two-year-response to growth hormone (rhGH) and the biochemical profile in patients with turner syndrome

Álvarez-Nava

Lanes

Quintero

et al. 2013

Int J Pediatr Endocrinol

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BackgroundIt is possible that genes on the X chromosome are expressed differently depending of its parental origin. The objective of this study was to determine the influence of the parental origin of the X-chromosome on phenotypic variability, response to rhGH and on the biochemical profile of TS patients.MethodsThis was a cross-sectional multicenter correlational study carried out over three years in six Latin-American university hospitals. Unrelated 45,X TS patients (n = 93; 18.3 ± 8.5 years )) were evaluated. A subgroup (n = 34) of the patients were prospectively treated with rhGH over two years. DNA profiles of patients and their mothers were compared to determine the parental origin of the retained X-chromosome through 10 polymorphic X-chromosome-STRs. The association with clinical features, biochemical profiles and anthropometric data at the beginning and after two years of rhGH treatment was determined.ResultsSeventy two percent of patients retained the maternal X chromosome (Xm). A trend towards significance between maternal height and patients final height (p ≤ 0.07) in 45,Xm subjects was observed. There was no correlation between paternal height and patient height. No differences were detected between both groups in regard to dysmorphic features, classical malformations or increase in the height-SDS after rhGH. There were higher levels of triglycerides, total and LDL cholesterol in patients >20 years who retained the Xm.ConclusionsThe parental origin of the retained X chromosome may influence lipid metabolism in TS patients, but its effect on growth seems to be minimal. No parental-origin-effect on the phenotypic features, associated anomalies and on the growth response to rhGH was found in 45,X TS individuals.

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Section: Methodsmentioning

confidence: 99%

Effect of the parental origin of the X-chromosome on the clinical features, associated complications, the two-year-response to growth hormone (rhGH) and the biochemical profile in patients with turner syndrome

Álvarez-Nava

Lanes

Quintero

et al. 2013

Int J Pediatr Endocrinol

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“…Three possible genotypes can be observed: fl/fl, fl/d3 and d3/d3, with the latter being the one with the lowest frequency. 18 Additionally, polymorphisms inherited from the VDR gene can affect IGF signaling and in turn, response to rhGH in patients with GH deficiency and TS. Four studies have investigated this SNP alone 15,17,19 and three, its role alone and in combination with polymorphisms in the VDR (vitamin D receptor), IGFBP3 (insulin-like growth factor binding protein) and SOCS2 (suppressor of cytokine signaling) genes, via gene-gene interaction.…”

Section: Short Staturementioning

confidence: 99%

“…The VDR gene is important for height because it interferes with calcium and phosphate homeostasis, influencing skeletal growth. 20,21 One of the studies 20 mentioned that the possible reasons for the lack of correlation in two previous studies included the small number of patients evaluated 18 and the fact that few individuals are carriers of the d3 allele. The polymorphisms −202 A/C IGFBP3 and SOCS-2 are involved in the pharmacogenetics of rhGH and negative regulation of GHR signaling, respectively.…”

Section: Short Staturementioning

confidence: 99%

“…20,21 In one of these studies, the authors suggest the use of these genetic markers to identify, among patients treated with rhGH, those genetically predisposed to have less favorable results. 17---19 One of them 18 reported that the study was limited by sample size. 17 Regarding growth, polymorphisms in the GHR gene contributed to therapy response alone 15 or in combination.…”

Section: Short Staturementioning

confidence: 99%

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Turner syndrome and genetic polymorphism: a systematic review

Marqui

2015

Revista Paulista de Pediatria (English Edition)

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Objective: To present the main results of the literature on genetic polymorphisms in Turner syndrome and their association with the clinical signs and the etiology of this chromosomal disorder. Data sources: The review was conducted in the PubMed database without any time limit, using the terms Turner syndrome and genetic polymorphism. A total of 116 articles were found, and based on the established inclusion and exclusion criteria 17 were selected for the review. Data synthesis: The polymorphisms investigated in patients with Turner syndrome were associated with growth deficit, causing short stature, low bone mineral density, autoimmunity and cardiac abnormalities, which are frequently found in patients with Turner syndrome. The role of single nucleotide polymorphisms in the etiology of Turner syndrome, i.e., in chromosomal nondisjunction, was also confirmed. Conclusions: Genetic polymorphisms appear to be associated with Turner syndrome. However, in view of the small number of published studies and their contradictory findings, further studies in different populations are needed in order to clarify the role of genetic variants in the clinical signs and etiology of the Turner syndrome. Síndrome de Turner; Polimorfismo genético; Síndrome de Turner e polimorfismo genético: uma revisão sistemática Resumo Objetivo: Apresentar os principais resultados dos estudos que investigaram polimorfismos genéticos em síndrome de Turner, bem como sua associação com alguns sinais clínicos e etiologia desse distúrbio cromossômico. DOI of original article: http://dx.ARTICLE IN PRESS +Model 2 Marqui ABT Hormônio do crescimento; Aneuploidia Fontes de dados: Revisão bibliográfica feita no PubMed, sem limite de período, com os seguintes termos: Turner syndrome and genetic polymorphism. Foram identificados 116 artigos e, de acordo com os critérios de inclusão e exclusão, 17 foram selecionados para leitura. Síntese dos dados: Os polimorfismos investigados em pacientes com síndrome de Turner estavam relacionados com déficit de crescimento, que causou baixa estatura, densidade mineral óssea baixa, autoimunidade e anomalias cardíacas, que podem estar presentes com frequências significativas nas pacientes. Também foi verificado o papel dos polimorfismos de único nucleotídeo (SNPs) na etiologia da síndrome de Turner, ou seja, na não disjunção cromossômica. Conclusões: Os polimorfismos genéticos parecem estar associados à síndrome de Turner. Entretanto, por conta dos poucos estudos publicados e dos achados contraditórios, pesquisas em diferentes populações são necessárias para esclarecer o papel dessas variantes genéticas para os sinais clínicos e a etiologia do distúrbio cromossômico.

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“…In Turner syndrome, Alvarez-Nava et al (2010 [24]) have prospectively assessed the influence of GHR and VDR gene polymorphisms on the response to rhGH therapy in Venezuelan children with growth hormone deficiency (GHD, n = 28) and Turner syndrome (TS, n = 25). After the first 2 years of rhGH treatment, clinical data in both GHD and TS patients were not different according GHR or VDR genotypes.…”

Section: Discussionmentioning

confidence: 99%

Analysis of vitamin D receptor gene (VDR) polymorphisms in Turner syndrome patients

Bianco

Verreschi

Oliveira

et al. 2011

Gynecological Endocrinology

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Individuals with Turner syndrome (TS) have increased risk for autoimmune diseases, especially thyroid abnormalities. The function of the vitamin D receptor (VDR) gene is influenced by several genetic polymorphisms which are associated with a susceptibility to a range of autoimmune diseases. Thus, we have hypothesized a possible relationship between thyroid abnormalities and VDR polymorphisms (ApaI/G1025-49T, TaqI/T1056C, FokI/T2C and BsmI G1024 + 283A) in TS patients. A case-control study was performed comprising 101 Brazilian women with TS and a control group consisting of 133 healthy fertile women without a history of autoimmune diseases. In TS group, 21.8% had Hashimoto's thyroiditis. Detection of VDR polymorphisms was performed using TaqMan system by real-time PCR. The χ(2) was used to compare allele and genotype frequencies between groups. Combined genotypes of VDR gene polymorphisms were assessed by the haplotype analysis. A p value <0.05 was considered statistically significant. Relatively similar VDR polymorphisms genotype and allelic frequencies in cases and controls were found, even when only considering the patients with thyroid abnormalities. Haplotype analysis showed that none of the VDR haplotypes were associated to thyroid diseases in TS patients. In conclusion, the results showed no association between VDR gene polymorphisms and thyroid abnormalities in Brazilian TS patients tested.

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GHR and VDR Genes do not Contribute to the Growth Hormone (GH) Response in GH Deficient and Turner Syndrome Patients

Cited by 10 publications

References 24 publications

Effect of the parental origin of the X-chromosome on the clinical features, associated complications, the two-year-response to growth hormone (rhGH) and the biochemical profile in patients with turner syndrome

Effect of the parental origin of the X-chromosome on the clinical features, associated complications, the two-year-response to growth hormone (rhGH) and the biochemical profile in patients with turner syndrome

Turner syndrome and genetic polymorphism: a systematic review

Analysis of vitamin D receptor gene (VDR) polymorphisms in Turner syndrome patients

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