Impact of IGF(CA)19 gene polymorphism on the metabolic response to GH therapy in adult GH-deficient patients C Giavoli 1,2 , E Profka 1,2 , E Sala 1,2 , M Filopanti 1,2 , A M Barbieri 1,2 , S Bergamaschi 1,2 , E Ferrante 1,2 , M Arosio 1,3 , B Ambrosi 4 , A G Lania 5,6 , A Spada 1,2 and P Beck-Peccoz 1,2 1 Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy, 2 Endocrinology and Diabetology Unit, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Via Francesco Sforza, 35, 20122 Milan, Italy, 3 Unit of Endocrine Diseases and Diabetology, Ospedale San Giuseppe, Multimedica, Milan, Italy, 4 Endocrinology and Diabetology Unit, Department of Medical and Surgical Sciences, University of Milan, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy 5 Biometra Department, University of Milan, and 6 Endocrine Unit, Humanitas Cinical and Research Center, Rozzano, 20089 Milan, Italy Correspondence should be addressed to C Giavoli Email claudiagiavoli@yahoo.it 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. European Journal of Endocrinology (2014) 170, 273–281 Introduction Growth hormone deficiency (GHD) in adults is a clinical syndrome characterized by several metabolic alterations such as increased body fat percentage (BF%), impaired physical performance, altered lipid profile, and insulin resistance. Many reports support efficacy of recombinant human GH (rhGH) replacement therapy in reversing most of the above-mentioned alterations (1, 2, 3). As suggested by recent guidelines (4), GH replacement in adults should be started with low doses, thereafter titrated and individualized according to insulin-like growth factor 1 (IGF1) levels and clinical conditions of the patients (4, 5), in order to obtain the best efficacy, minimizing side- effects. Nowadays, it is well established that the individual response to rhGH is highly variable and, in the last years, European Journal of Endocrinology Clinical Study C Giavoli and others IGF1 promoter polymorphism in GHD adults 170 :2 273–281 www.eje-online.org Ñ 2014 European Society of Endocrinology DOI: 10.1530/EJE-13-0600 Printed in Great Britain Published by Bioscientifica Ltd. Downloaded from Bioscientifica.com at 06/03/2020 04:04:42PM via free access