Growth hormone receptor d3-variant, insulin-like growth factor binding protein-1 -575G/A polymorphism and postnatal catch-up growth: association with parameters of glucose homeostasis in former extremely low birth weight preterm infants.
BACKGROUND
Low birth weight predisposes to the development of insulin resistance. In addition to auxological parameters such as rapid catch-up growth, low IGFBP-1 serum levels in childhood have been linked to an increased risk of insulin resistance later in life. Concerning postnatal growth, we previously reported the GHRd3-variant to be associated with catch-up growth in preterm infants. In children born small for gestational age, a common IGFBP-1 promoter polymorphism -575G/A has been linked to IGFBP-1 serum levels and has been suggested to be an additional player in the interaction between the IGF-IGFBP-axis and metabolism.


METHODS
We analyzed postnatal growth, metabolic parameters, and genotypes for the GHRd3-variant and IGFBP-1 -575G/A in 51 former extremely low birth weight preterm infants (mean age 5.9 years).


RESULTS
GHRd3 but not IGFBP-1 -575G/A was significantly associated with postnatal growth velocity. Catch-up growth, GHRd3, and IFGBP-1 -575G/A did not influence fasting insulin or HOMA-IR. However, we found significantly higher HbA1c and lower IGFBP-1 concentrations in GHRd3-carriers, a finding not seen with respect to IGFBP-1 -575G/A. Interestingly, HbA1c and IGFBP-1 levels also did not differ between children either with or without catch-up growth.


CONCLUSIONS
In addition to an association with catch-up growth, GHR exon 3 genotype significantly modulates HbA1c and IGFBP-1 concentrations in former ELBW infants. In order to confirm this observation and to clarify whether the GHRd3-variant might be considered as an independent modulator of the low birth weight infant's risk to develop insulin resistance later in life, larger studies extending to later ages are required.
Pediatric Endocrinology Division, Children's Hospital, University of Bonn, Germany.
Felix
F
Schreiner
Bettina
B
Gohlke
Sonja
S
Stutte
Peter
P
Bartmann
Joachim
J
Woelfle
D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002657:Child Development / Q000502:physiology; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D005947:Glucose / Q000378:metabolism*; D006442:Glycated Hemoglobin / Q000032:analysis; D006706:Homeostasis / Q000235:genetics / Q000502:physiology; D006801:Humans; D052577:Infant, Extremely Low Birth Weight / Q000097:blood / Q000254:growth & development* / Q000378:metabolism / Q000502:physiology; D007231:Infant, Newborn; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood / Q000235:genetics*; D008297:Male; D036801:Parturition / Q000502:physiology; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology
D002352:Carrier Proteins; D005947:Glucose; D006442:Glycated Hemoglobin; D018970:Insulin-Like Growth Factor Binding Protein 1; D020033:Protein Isoforms; C032231:IGFBP1 protein, human; C517652:hemoglobin A1c protein, human; C051815:somatotropin-binding protein