Abstract Objective: A polymorphism in the promoter region of the IGF1 gene has been linked to serum IGF1 levels, risk of diabetes, and cardiovascular diseases with conflicting results. The aim of this study was to investigate the impact of this polymorphism on the short-term (1 year, nZ98) and long-term (5 years, nZ50) metabolic response to recombinant human GH (rhGH) in GH-deficient (GHD) adults. Design and methods: Prospective study on GHD adults. Different genotypes were studied by microsatellite method. According to the most frequent 192 bp allele (19 cytosine-Adenosine-repeats), subjects were divided into homozygous (19/19), heterozygous (19/X), and noncarriers (X/X). Results: Basal characteristics of patients as well as their response to rhGH in terms of decrease in body fat percentage and increase in IGF1 levels were not different in the three genotype-groups. Conversely, after 1-year rhGH, a significant worsening of insulin sensitivity (i.e. increase in fasting glucose levels and homeostasis model assessment of insulin resistance) and a significant improvement in lipid profile (i.e. reduction in total cholesterol and LDL-cholesterol) were recorded only in homozygous subjects. In the long-term, insulin sensitivity was restored in all the patients, while a significant improvement in lipid profile was observed in homozygous and heterozygous subjects, but not in noncarrier subjects. No difference in rhGH dose among groups was recorded throughout the study. Conclusions: In GHD adults, the presence of the WT allele in the IGF1 gene promoter may enhance sensitivity to either negative or positive metabolic changes induced by rhGH.

Impact of IGF(CA)19 gene polymorphism on the metabolic response to GH therapy in adult GH-deficient patients / C. Giavoli, E. Profka, E. Sala, M. Filopanti, A.M. Barbieri, S. Bergamaschi, E. Ferrante, M. Arosio, B. Ambrosi, A.G. Lania, A. Spada, P. Beck-Peccoz. - In: EUROPEAN JOURNAL OF ENDOCRINOLOGY. - ISSN 0804-4643. - 170:2(2014 Feb), pp. 273-281.

Impact of IGF(CA)19 gene polymorphism on the metabolic response to GH therapy in adult GH-deficient patients

C. Giavoli
Primo
;
E. Profka
Secondo
;
E. Sala;M. Filopanti;A.M. Barbieri;S. Bergamaschi;E. Ferrante;M. Arosio;B. Ambrosi;A.G. Lania;A. Spada
;
2014

Abstract

Abstract Objective: A polymorphism in the promoter region of the IGF1 gene has been linked to serum IGF1 levels, risk of diabetes, and cardiovascular diseases with conflicting results. The aim of this study was to investigate the impact of this polymorphism on the short-term (1 year, nZ98) and long-term (5 years, nZ50) metabolic response to recombinant human GH (rhGH) in GH-deficient (GHD) adults. Design and methods: Prospective study on GHD adults. Different genotypes were studied by microsatellite method. According to the most frequent 192 bp allele (19 cytosine-Adenosine-repeats), subjects were divided into homozygous (19/19), heterozygous (19/X), and noncarriers (X/X). Results: Basal characteristics of patients as well as their response to rhGH in terms of decrease in body fat percentage and increase in IGF1 levels were not different in the three genotype-groups. Conversely, after 1-year rhGH, a significant worsening of insulin sensitivity (i.e. increase in fasting glucose levels and homeostasis model assessment of insulin resistance) and a significant improvement in lipid profile (i.e. reduction in total cholesterol and LDL-cholesterol) were recorded only in homozygous subjects. In the long-term, insulin sensitivity was restored in all the patients, while a significant improvement in lipid profile was observed in homozygous and heterozygous subjects, but not in noncarrier subjects. No difference in rhGH dose among groups was recorded throughout the study. Conclusions: In GHD adults, the presence of the WT allele in the IGF1 gene promoter may enhance sensitivity to either negative or positive metabolic changes induced by rhGH.
rGH therapy ; GH deficiency ; IGF1 gene ; polymorphism ; glucose metabolism ; cardiovascular risk factors
Settore MED/13 - Endocrinologia
Article (author)
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/232365
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 4
  • ???jsp.display-item.citation.isi??? 4
social impact