The -G1245A IGF1 polymorphism is related with small head size and less brain sparing in small for gestational age born children

Eur J Endocrinol. 2009 Apr;160(4):549-55. doi: 10.1530/EJE-08-0647. Epub 2009 Jan 15.


Context: 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.

Design: Gene association study.

Patients: We studied 635 SGA subjects out of which 439 remained short and 196 had a postnatal height >-2.00 SDS.

Measurements: 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.

MeSH terms

  • Adolescent
  • Alleles
  • Birth Weight / physiology
  • Brain / anatomy & histology*
  • Child
  • Cohort Studies
  • DNA / genetics
  • Female
  • Genotype
  • Head / anatomy & histology*
  • Humans
  • Infant
  • Infant, Newborn
  • Infant, Small for Gestational Age / physiology*
  • Insulin-Like Growth Factor I / genetics*
  • Male
  • Polymorphism, Genetic / genetics*
  • Polymorphism, Single Nucleotide
  • Young Adult


  • Insulin-Like Growth Factor I
  • DNA