Birth Size, Postnatal Growth and Growth during Growth Hormone Treatment in Small-for-Gestational-Age Children: Associations with <i>IGF1</i> 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. 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.

Insulin-like growth factor 1 gene (CA)n repeats and a variable number of tandem repeats of the insulin gene in Brazilian children born small for gestational age

“…Our findings suggest that the genetic factors that determine permanent short stature in children born SGA are mainly of paternal origin; this phenomenon has been previously described in the literature (46). …”

“…In another study, four IGF1 gene polymorphisms were analyzed in 201 short-SGA children (46), and no association of CA repeats with birth size or postnatal growth was observed (Table 1). …”

Growth and body composition in very young SGA children

“…The Swedish Study Group for Growth Hormone Treatment shows better catch-up growth in shorter and younger SGA children [45], although the absence of association between gestational age-adjusted birth size, height, and weight standard deviation score (SDS) and growth during GH treatment has been reported [46]. Recently, Ester et al have shown that the −G1245A single nucleotide polymorphism in the IGF-I gene appears to be a marker for the well known −841(CA) n /192 bp polymorphism [46].…”

“…Recently, Ester et al have shown that the −G1245A single nucleotide polymorphism in the IGF-I gene appears to be a marker for the well known −841(CA) n /192 bp polymorphism [46]. Furthermore, a polymorphic variation in the IGFBP-3 promoter region has been correlated with IGFBP-3 levels, spontaneous growth, and response to GH treatment in children born SGA [47].…”

GH-IGF-IGFBP Axis and Metabolic Profile in Short Children Born Small for Gestational Age

“…Twin studies have shown that 40-65% of interindividual variability in IGF-I, IGF-II and IGFBP-3 levels is genetically determined (Harrela et al, 1996). Single nucleotide polymorphisms in the IGF-I gene are correlated with IGF-I levels, head circumference in short SGA children, birth weight and increased risk of type 2 diabetes and ischemic heart disease, although not all studies found similar associations (Ester et al, 2009b;Frayling et al, 2002;Johnston et al, 2003;Vaessen et al, 2001). …”