Genetic markers of insulin sensitivity and insulin secretion are associated with spontaneous postnatal growth and response to growth hormone treatment in short SGA children: the North European SGA Study (NESGAS)

Rikke Beck Jensen, Ajay Thankamony, Felix Day, Robert A Scott, Claudia Langenberg, Jeremy Kirk, Malcolm Donaldson, Sten-A Ivarsson, Olle Söder, Edna Roche, Hilary Hoey, Anders Juul, Ken K Ong, David B Dunger

11 Citationer (Scopus)

Abstract

Purpose: The wide heterogeneity in the early growth and metabolism of children born small for gestational age (SGA), both before and during growth hormone (GH) therapy, may reflect common genetic variations related to insulin secretion or sensitivity. Method: Combined multi-allele single nucleotide polymorphism (SNP) scores with known associations with insulin sensitivity or insulin secretion were analysed for their relationships with spontaneous postnatal growth and first year responses to GH therapy in 96 short SGA children. Results: The insulin sensitivity allele score (GS-InSens) was positively associated with spontaneous postnatal weight gain (B:0.12 SD scores per allele, 95% CI:0.01-0.23, p=0.03) and also in response to GH therapy with first year height velocity (0.18 cm/year per allele, 0.02-0.35, p=0.03) and change in IGF-I (0.17 SD scores per allele, 0.00-0.32, p=0.03). The association with first year height velocity was independent of reported predictors of response to GH therapy (adjusted p=0.04). The insulin secretion allele score (GS-InSec) was positively associated with spontaneous postnatal height gain (0.15, 95% CI:0.01-0.30, p=0.03) and disposition index both before (0.02, 0.00-0.04, p=0.04) and after 1-year of GH therapy (0.03, 0.01-0.05, p=0.002), but not with growth and IGF-I responses to GH therapy. Neither allele scores were associated with size at birth. Conclusion: Genetic allele scores indicative of insulin sensitivity and insulin secretion were associated with spontaneous postnatal growth and responses to GH therapy. Further pharmacogenetic studies may support the rationale for adjuvant therapies by informing the mechanisms of treatment response.

OriginalsprogEngelsk
TidsskriftThe Journal of clinical endocrinology and metabolism
Sider (fra-til)jc20143469
ISSN0021-972X
DOI
StatusUdgivet - 12 dec. 2014

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