title: Birth size, postnatal growth and growth during growth hormone treatment in small-for-gestational-age children: associations with IGF1 gene polymorphisms and haplotypes?
abstract: BACKGROUND
  Short small-for-gestational-age (SGA) children experience pre- and postnatal growth restriction, which might be influenced by polymorphisms in the IGF1 gene. The well-known -841(CA)(n)/192 bp polymorphism has been associated with birth size and cardiovascular disease.
  
  
  OBJECTIVE
  To determine whether birth size, postnatal growth and growth during growth hormone (GH) treatment, were associated with IGF1 gene polymorphisms and haplotypes.
  
  
  METHODS
  201 short SGA children were investigated for four IGF1 gene polymorphisms in the promoter (-G1245A, -841(CA)(n)), intron 2 (+3703(CT)(n)) and 3UTR (+A1830G). Spontaneous growth and growth during GH treatment were studied.
  
  
  RESULTS
  The -1245 A allele was identified as a marker-allele for the well-known -841(CA)(n)/non-192 bp allele, both part of haplotype 2. The -1245 A allele was not associated with head circumference at birth, but was associated with a postnatal 0.3 SDS smaller head circumference at age 1-3. The -1245 A allele was also associated with a 1-week shorter gestational age which explained the association with a smaller absolute birth size. No associations were found with gestational age-adjusted birth size, height and weight SDS during postnatal life and with growth during GH treatment.
  
  
  CONCLUSIONS
  The -G1245A SNP appeared to be a marker for the well-known -841(CA)(n)/192 bp polymorphism. Haplotype 2, of which the -1245 A allele was the marker, was associated with a smaller head circumference SDS during spontaneous postnatal growth, but not during GH treatment.
authors: Department of Pediatrics, Division of Endocrinology, Erasmus MC-Sophia Children's Hospital, Erasmus MC, Rotterdam, The Netherlands. w.ester@erasmusmc.nl
authors: Wietske A
authors: WA
authors: Ester
authors: Joyce B
authors: JB
authors: van Meurs
authors: Nicolette J
authors: NJ
authors: Arends
authors: André G
authors: AG
authors: Uitterlinden
authors: Maria A
authors: MA
authors: de Ridder
authors: Anita C
authors: AC
authors: Hokken-Koelega
mesh_terms: D001724:Birth Weight; D002648:Child; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D019382:Human Growth Hormone / Q000627:therapeutic use*; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age / Q000254:growth & development*; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic; D011446:Prospective Studies
chemical_list: D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I