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. 2022 Jun 13:13:897897.
doi: 10.3389/fendo.2022.897897. eCollection 2022.

GH Responsiveness Is not Correlated to IGF1 P2 Promoter Methylation in Children With Turner Syndrome, GHD and SGA Short Stature

Anja Apel  1 , Daniel I Iliev  1 , Christina Urban  1 , Karin Weber  1 , Roland Schweizer  1 , Gunnar Blumenstock  2 , Sarah Pasche  3 , Vanessa Nieratschker  3 , Gerhard Binder  1
Affiliations

GH Responsiveness Is not Correlated to IGF1 P2 Promoter Methylation in Children With Turner Syndrome, GHD and SGA Short Stature

Anja Apel et al. Front Endocrinol (Lausanne). .

Erratum in

Abstract

Background: The methylation of IGF1 promoter P2 was reported to negatively correlate with serum IGF-1 concentration and rhGH treatment response in children with idiopathic short stature. These findings have not yet been confirmed.

Objective: This study aimed to determine IGF1 promoter P2 methylation in short children treated with rhGH and correlate clinical parameters with the methylation status. In addition, long-term stability of methylation during rhGH treatment was studied.

Design: This was a single tertiary center study analyzing clinical GH response and IGF-1 serum concentration changes in patients with GHD (n=40), SGA short stature (n=36), and Turner syndrome (n=16) treated with rhGH. Data were correlated to the methylation of two cytosine residues (-137, +97) of the P2 promoter of IGF1 in blood cells measured by pyrosequencing in 443 patient samples.

Results: Basal and stimulated IGF-1 concentrations, first year increment in height velocity and studentized residuals of a prediction model did not correlate to the methylation of -137 und +97 in IGF1 P2 promoter. The methylation of these two sites was relatively stable during treatment.

Conclusions: This study did not confirm IGF1 P2 promotor being a major epigenetic locus for GH responsiveness in patients treated with a normal dose of rhGH. Additional studies are warranted.

Keywords: GH response; GH treatment; IGF-1; prediction; promotor methylation; short stature.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Longitudinal course of IGF1 P2 methylation at position -137 in blood of children with GHD, SGA short stature and Turner syndrome treated with rhGH. Filled symbols indicate patients with exon3-deleted GHR.
Figure 2
Figure 2
First year height velocity increment (1st y HV increment) and IGF1 P2 methylation at position -137 in blood of children with GHD, SGA short stature and Turner syndrome treated with rhGH. Filled symbols indicate patients with exon3-deleted GHR allele.
Figure 3
Figure 3
Studentized residuals of first year height prediction and IGF1 P2 methylation at position -137 in blood of children with GHD, SGA short stature and Turner syndrome treated with rhGH. Filled symbols indicate patients with exon3-deleted GHR allele.
Figure 4
Figure 4
Baseline IGF-1 SDS and IGF1 P2 methylation at position -137. Filled symbols indicate patients with exon3-deleted GHR allele.
Figure 5
Figure 5
GH-induced increment in IGF-1 SDS (Delta IGF-1 SDS) and IGF1 P2 methylation at position -137. Filled symbols indicate patients with exon3-deleted GHR allele.
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