D3-Growth hormone receptor polymorphism in acromegaly: Effects on metabolic phenotype

Laura Montefusco, Marcello Filopanti, Cristina L. Ronchi, Luca Olgiati, Carmen La-Porta, Marco Losa, Paolo Epaminonda, Francesca Coletti, Paolo Beck-Peccoz, Anna Spada, Andrea G. Lania, Maura Arosio

Research output: Contribution to journalArticlepeer-review


Objective A common polymorphic variant of the growth hormone receptor (GHR) is because of genomic deletion of exon 3 and has been linked with increased responsiveness to exogenous GH. The impact of this polymorphism in acromegaly, a disease characterized by endogenous excess of GH and partial loss of IGF-I feedback on tumoural GH secretion, is not clear. The aim of this study was to investigate possible influences of d3GHR on the GH/IGF-I relationship and metabolic parameters in acromegaly. Design and methods Retrospective study on 76 acromegalic patients. Genotype analysis was carried out on leucocyte DNA by multiplex PCR assay. Clinical, hormonal and biochemical parameters at diagnosis were collected from patients' medical records. Results Forty-two patients (55·3%) were homozygotes for the allele encoding the full-length GHR (fl/flGHR), 27 patients were heterozygotes (fl/d3) and seven homozygotes (d3/d3) for the genomic deletion of exon 3. Heterozygotes and homozygotes for the d3 allele were considered together (d3GHR) and compared with fl/flGHR patients. d3GHR and fl/flGHR patients showed no difference in GH and IGF-I levels or in the relationship between these two parameters. Patients bearing d3GHR had a lower body mass index (BMI) than patients bearing fl/flGHR (25·8 ± 2·1 vs. 28·1 ± 4·8 kg/m2, P <0·05). Diabetes mellitus and hypertension were equally distributed, but more d3GHR patients had a normal glucose tolerance (66·7%vs. 56·3%, P <0·05). The presence of d3GHR allele, and not BMI or age, was a significant negative predictor of insulin levels 120 min after oral glucose load (β = -80·8, P <0·05). Conclusions This study supports the hypothesis that the d3GHR is functionally different from the fl/fl variant mostly for the effects on body weight regulation and on glucose metabolism.

Original languageEnglish
Pages (from-to)661-667
Number of pages7
JournalClinical Endocrinology
Issue number5
Publication statusPublished - May 2010

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism


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