Background: There is wide heterogeneity in responses to GH treatment in children born small for gestational age (SGA).
Objective and Hypotheses: The aim was to explore the impact of genetic markers on glucose metabolism and growth during first year high-dose GH treatment in SGA children.
Method: In North European Small for Gestational Age Study (NESGAS) patients received high-dose GH (67 μg/kg per day) the first year. 97 patients were genotyped using the Metabochip a custom Illumina iSelect genotyping array enriched for single nucleotide polymorphisms (SNPs) associated with growth and metabolic traits. Combined multi-allele gene scores were generated comprising ten SNPs for insulin resistance (GS-IR) and 18 SNPs for insulin secretion (GS-IS).
Results: Higher GS-IR was associated with shorter height (B: −0.08 SDS/allele, 95% CI: −0.15 to 0, P=0.048) and lower weight (B: −0.10, 95% CI: −0.20 to −0.003, P=0.04) after 1 year of treatment (corrected for age, sex and mid-parental height). GS-IR was inversely associated with first year change in IGF1 (B: −0.16 SDS/allele, 95% CI: −0.29 to −0.02, P<0.03). GS-IR added significantly to the Ranke SGA growth prediction model, adding 8% to the variance explained in growth response (independent effect of GS-IR: B: −0.20, 95% CI: −0.38 to −0.02, P=0.03).
GS-IS was associated with increased insulin secretion (IVGTT) (corrected for age, sex, and BMI) at baseline (B: 0.03, 95% CI: 0.0040.05, P=0.02) and 1 year (B: 0.03, 95% CI: 0.0050.05, P=0.02). There was no association to HOMA-S, but GS-IS was positively associated with Disposition Index at baseline (B: 0.03, 95% CI: 0.0040.05, P=0.02) and 1 year (B: 0.03, 95% CI: 0.010.05, P=0.002).
Conclusion: Increased genetic susceptibility to insulin resistance was associated with lower height and IGF1 responses to GH treatment in SGA children. Higher scores of insulin secretion alleles corresponded to increased insulin secretion and increased disposition index. These novel results highlight the potential role of genetic factors in defining the response of treatment in SGA patients.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology