title: The -G1245A IGF1 polymorphism is related with small head size and less brain sparing in small for gestational age born children.
abstract: BACKGROUND
  Small for gestational age (SGA) subjects 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, cardiovascular disease, and IGF-1 levels, and is in linkage disequilibrium with the -G1245A single nucleotide polymorphism (SNP; rs35767).
  
  
  OBJECTIVE
  To associate the -G1245A SNP with head circumference (HC) and brain sparing (a greater head compared with height SDS) in short SGA and SGA catch-up subjects.
  
  
  METHODS
  Gene association study.
  
  
  METHODS
  We studied 635 SGA subjects out of which 439 remained short and 196 had a postnatal height >-2.00 SDS.
  
  
  METHODS
  The -G1245A SNP IGF1 gene polymorphism and head size.
  
  
  RESULTS
  All SGA subjects had a postnatal head size below the population mean (-1.01 SDS, P<0.001). Whereas SGA catch-up subjects had a head size that was in proportion with their height, short SGA subjects displayed extensive brain sparing (HC - height: SGA CU: 0.01 versus short SGA: 1.75 SDS, P<0.001). The most severely SGA born subjects had a 0.4 SDS smaller postnatal head size and 0.6 SDS less brain sparing when carrying the -1245 A-allele in contrast to G-allele carriers (P=0.03). The association between the -G1245A SNP and head size remained significant after correction for birth weight and postnatal height SDS (P=0.03). Birth weight, birth length and postnatal height SDS were not related with the - G1245A SNP.
  
  
  CONCLUSIONS
  The -1245 A-allele of the IGF1 promoter SNP is associated with a small head size and less brain sparing in SGA born subjects and particularly those with the lowest birth weight.
authors.affiliation: Division of Endocrinology, Department of Pediatrics, Erasmus MC/Sophia Children's Hospital, Rotterdam, The Netherlands. w.ester@erasmusmc.nl
authors.forename: Wietske A
authors.initials: WA
authors.lastname: Ester
authors.forename: Joyce B
authors.initials: JB
authors.lastname: van Meurs
authors.forename: Nicolette J
authors.initials: NJ
authors.lastname: Arends
authors.forename: André G
authors.initials: AG
authors.lastname: Uitterlinden
authors.forename: Maria A
authors.initials: MA
authors.lastname: de Ridder
authors.forename: Anita C
authors.initials: AC
authors.lastname: Hokken-Koelega
mesh_terms: D000293:Adolescent; D000483:Alleles; D001724:Birth Weight / Q000502:physiology; D001921:Brain / Q000033:anatomy & histology*; D002648:Child; D015331:Cohort Studies; D004247:DNA / Q000235:genetics; D005260:Female; D005838:Genotype; D006257:Head / Q000033:anatomy & histology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: D007334:Insulin-Like Growth Factor I; D004247:DNA