Influence of the d3GH receptor polymorphism on the metabolic and biochemical phenotype of GH-deficient adults at baseline and during short- and long-term recombinant human GH replacement therapy.
OBJECTIVE
A common polymorphic variant of GH receptor (exon 3 deletion, d3GHR) has been linked with increased response to recombinant human GH (rhGH) in some patients with or without GH deficiency (GHD). The aim of the study was to investigate the impact of the GHR genotype on the phenotype of GHD adults and on the metabolic effect of rhGH therapy.


METHODS
Prospective study of GHD patients evaluated before and during short- (1 year, n=100) and long-term (5 years, n=50) rhGH therapy.


METHODS
Effects of rhGH on IGF1 levels, body composition (body fat percentage, BF%), body mass index, lipid profile, and glucose homeostasis (fasting insulin and glucose, insulin sensitivity indexes) were evaluated according to the presence or the absence of the d3GHR variant.


RESULTS
The different genotype did not influence basal phenotype of GHD. Short-term rhGH determined normalization of IGF1 levels, decrease in BF%, and worsening of insulin sensitivity, independently from the presence of the d3GHR allele. A significant increase in high-density lipoprotein cholesterol occurred in the d3GHR group. Normalization of IGF1 levels and decrease in BF% were maintained after 5 years. Insulin sensitivity restored to basal values, though in d3GHR patients fasting glucose remained significantly higher than at baseline. After both 1 and 5 years, percentage of subjects with impaired glucose tolerance, similar in the two groups at baseline, decreased in fl/fl while doubled in d3GHR patients. In this last group, a long-term significant reduction in total and low-density lipoprotein cholesterol was also observed.


CONCLUSIONS
The functional difference of d3GHR may influence some metabolic effects of rhGH on GHD adults.
Giavoli
Claudia
C
Department of Medical Sciences, University of Milan, Milan, Italy. claudiagiavoli@yahoo.it
Ferrante
Emanuele
E
Profka
Eriselda
E
Olgiati
Luca
L
Bergamaschi
Silvia
S
Ronchi
Cristina L
CL
Verrua
Elisa
E
Filopanti
Marcello
M
Passeri
Elena
E
Montefusco
Laura
L
Lania
Andrea G
AG
Corbetta
Sabrina
S
Arosio
Maura
M
Ambrosi
Bruno
B
Spada
Anna
A
Beck-Peccoz
Paolo
P
D000328:Adult; D000367:Age Factors; D004334:Drug Administration Schedule; D004393:Dwarfism, Pituitary / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D005260:Female; D017353:Gene Deletion; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000172:deficiency* / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*; D011446:Prospective Studies; D011986:Receptors, Somatotropin / Q000235:genetics* / Q000502:physiology; D013997:Time Factors
D011986:Receptors, Somatotropin; D019382:Human Growth Hormone