Impact of IGF(CA)19 gene polymorphism on the metabolic response to GH therapy in adult GH-deficient patients.
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, n=98) and long-term (5 years, n=50) metabolic response to recombinant human GH (rhGH) in GH-deficient (GHD) adults.


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.
Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
C
C
Giavoli
E
E
Profka
E
E
Sala
M
M
Filopanti
A M
AM
Barbieri
S
S
Bergamaschi
E
E
Ferrante
M
M
Arosio
B
B
Ambrosi
A G
AG
Lania
A
A
Spada
P
P
Beck-Peccoz
D000328:Adult; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D020249:Hormone Replacement Therapy; D019382:Human Growth Hormone / Q000172:deficiency* / Q000627:therapeutic use*; D006801:Humans; D007333:Insulin Resistance; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000235:genetics*; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000627:therapeutic use
D008055:Lipids; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I