Birth size, postnatal growth and growth during growth hormone treatment in small-for-gestational-age children: associations with IGF1 gene polymorphisms and haplotypes?

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.

Aims: 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.