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)
Jensen, Rikke Beck
Journal of Clinical Endocrinology & Metabolism
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Jensen, R. B., Thankamony, A., Day, F., Scott, R., Langenberg, C., Kirk, J., Donaldson, M., et al. (2014). 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). Journal of Clinical Endocrinology & Metabolism, 100 https://doi.org/10.1210/jc.2014-3469
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 1st 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 1st 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 1st 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.
Small for gestational age, Growth hormone therapy, Genetic markers, Insulin sensitivity, Insulin secretion
This study was funded by a research grant from The Danish Council for Independent Research/ Medical Sciences and a research grant from Novo Nordisk A/S.
British Society for Paediatric Endocrinology and Diabetes (BSPED) (unknown)
External DOI: https://doi.org/10.1210/jc.2014-3469
This record's URL: https://www.repository.cam.ac.uk/handle/1810/249247