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  • Title: Birth size, postnatal growth and growth during growth hormone treatment in small-for-gestational-age children: associations with IGF1 gene polymorphisms and haplotypes?
    Author: Ester WA, van Meurs JB, Arends NJ, Uitterlinden AG, de Ridder MA, Hokken-Koelega AC.
    Journal: Horm Res; 2009; 72(1):15-24. PubMed ID: 19571555.
    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. 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.
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