Growth hormone dose in growth hormone-deficient adults is not associated with IGF-1 gene polymorphisms.
OBJECTIVE
Several SNPs and a microsatellite cytosine-adenine repeat promoter polymorphism of the IGF-1 gene have been reported to be associated with circulating IGF-1 serum concentrations. Variance in IGF-1 concentrations due to genetic variations may affect different response to growth hormone (GH) treatment, resulting in different individually required GH-doses in GH-deficient patients. The aim of this study was to test if the IGF-1 gene polymorphisms are associated with the GH-dose of GH-deficient adults.


METHODS
A total of nine tagging SNPs, five additionally selected SNPs and a cytosine-adenine repeat polymorphism were determined in 133 German adult patients (66 men, 67 women; mean age 45.4 years +/- 13.1 standard deviation; majority Caucasian) with GH-deficiency (GHD) of different origin, derived from the prospective Pfizer International Metabolic Study (KIMS) Pharmacogenetics Study. Patients received GH-treatment for 12 months with finished dose-titration of GH and centralized IGF-1 measurements. GH-dose after 1 year of treatment, IGF-1 concentrations, IGF-1-standard deviation score (SDS), the IGF-1:GH ratio and anthropometric data were analyzed by genotype.


RESULTS
Except for rs1019731, which showed a significant difference of IGF-1-SDS by genotypes (p = 0.02), all polymorphisms showed no associations with the GH-doses, IGF-1 concentrations, IGF-1-SDS and IGF-1:GH ratio after adjusting for the confounding variables gender, age and BMI.


CONCLUSIONS
IGF-1 gene polymorphisms were not associated with the responsiveness to exogenous GH in GHD. Therefore, genetic variations of the IGF-1 gene seem not to be major influencing factors of the GH-IGF-axis causing variable response to exogenous GH-treatment.
Meyer
Silke
S
Division of Endocrinology & Diabetology, University Hospital Giessen and Marburg GmbH, Philipps-University Marburg, Baldingerstrasse, 35033 Marburg, Germany. meyersi@med.uni-marburg.de
Schaefer
Stephan
S
Ivan
Diana
D
Stolk
Lisette
L
Arp
Pascal
P
Uitterlinden
André G
AG
Nawroth
Peter P
PP
Plöckinger
Ursula
U
Stalla
Günter K
GK
Tuschy
Ulrich
U
Weber
Matthias M
MM
Weise
Alexander
A
Pfützner
Andreas
A
Kann
Peter H
PH
D000328:Adult; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D019382:Human Growth Hormone / Q000172:deficiency* / Q000627:therapeutic use*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism; D007438:Introns; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic
D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I