title: 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).
abstract: OBJECTIVE
  The wide heterogeneity in the early growth and metabolism of children born small for gestational age (SGA), both before and during GH therapy, may reflect common genetic variations related to insulin secretion or sensitivity.
  
  
  METHODS
  Combined multiallele single nucleotide polymorphism scores with known associations with insulin sensitivity or insulin secretion were analyzed 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 (regression coefficient [B]: 0.12 SD scores per allele; 95% confidence interval [CI], 0.01-0.23; P = .03) and also in response to GH therapy with first-year height velocity (B: 0.18 cm/y per allele; 95% CI, 0.02-0.35; P = .03) and change in IGF-1 (B: 0.17 SD scores per allele; 95% CI, 0.00-0.32; P = .03). The association with first-year height velocity was independent of reported predictors of response to GH therapy (adjusted P = .04). The insulin secretion allele score (GS-InSec) was positively associated with spontaneous postnatal height gain (B: 0.15; 95% CI, 0.01-0.30; P = .03) and disposition index both before (B: 0.02; 95% CI, 0.00-0.04; P = .04) and after 1 year of GH therapy (B: 0.03; 95% CI, 0.01-0.05; P = .002), but not with growth and IGF-1 responses to GH therapy. Neither of the allele scores was associated with size at birth.
  
  
  CONCLUSIONS
  Genetic allele scores indicative of insulin sensitivity and insulin secretion were associated with spontaneous postnatal growth and responses to GH therapy in short SGA children. Further pharmacogenetic studies may support the rationale for adjuvant therapies by informing the mechanisms of treatment response.
authors.affiliation: Department of Growth and Reproduction (R.B.J., A.J.), Rigshospitalet, University of Copenhagen, DK-2100 Copenhagen, Denmark; Department of Pediatrics (R.B.J., A.T., D.B.D.), Addenbrooke's Hospital, University of Cambridge, Cambridge CB2 0QQ, United Kingdom; Medical Research Council, Epidemiology Unit (F.D., R.A.S., C.L., K.K.O.), Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge CB2 0QQ, United Kingdom; Department of Endocrinology (J.K.), Birmingham Children's Hospital, Birmingham B4 6NH, United Kingdom; Department of Endocrinology (M.D.), Royal Hospital for Sick Children, Glasgow G3 8SJ, United Kingdom; Department of Clinical Sciences (S.I.), Endocrine and Diabetes Unit, University of Lund, SE-205 02 Malmö, Sweden; Pediatric Endocrinology Unit (O.S.), Department of Women's and Children's Health, Karolinska Institutet and University Hospital, 171 76 Stockholm, Sweden; and Department of Pediatrics (E.R., H.H.), The National Children's Hospital, University of Dublin, Trinity College, Dublin, Ireland.
authors.forename: Rikke Beck
authors.initials: RB
authors.lastname: Jensen
authors.forename: Ajay
authors.initials: A
authors.lastname: Thankamony
authors.forename: Felix
authors.initials: F
authors.lastname: Day
authors.forename: Robert A
authors.initials: RA
authors.lastname: Scott
authors.forename: Claudia
authors.initials: C
authors.lastname: Langenberg
authors.forename: Jeremy
authors.initials: J
authors.lastname: Kirk
authors.forename: Malcolm
authors.initials: M
authors.lastname: Donaldson
authors.forename: Sten-A
authors.initials: SA
authors.lastname: Ivarsson
authors.forename: Olle
authors.initials: O
authors.lastname: Söder
authors.forename: Edna
authors.initials: E
authors.lastname: Roche
authors.forename: Hilary
authors.initials: H
authors.lastname: Hoey
authors.forename: Anders
authors.initials: A
authors.lastname: Juul
authors.forename: Ken K
authors.initials: KK
authors.lastname: Ong
authors.forename: David B
authors.initials: DB
authors.lastname: Dunger
mesh_terms: D001827:Body Height / Q000187:drug effects / Q000235:genetics; D002657:Child Development / Q000187:drug effects; D005060:Europe; D005260:Female; D005819:Genetic Markers; D006130:Growth Disorders / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D019382:Human Growth Hormone / Q000627:therapeutic use*; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age / Q000254:growth & development* / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000235:genetics*; D000078790:Insulin Secretion; D008297:Male; D016896:Treatment Outcome
chemical_list: D005819:Genetic Markers; D007328:Insulin; D019382:Human Growth Hormone