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

Abstract

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 K841(CA) n /192 bp polymorphism has been associated with birth size, cardiovascular disease, and IGF-1 levels, and is in linkage disequilibrium with the KG1245A single nucleotide polymorphism (SNP; rs35767). Objective: To associate the KG1245A 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 OK2.00 SDS. Measurements: The KG1245A SNP IGF1 gene polymorphism and head size. Results: All SGA subjects had a postnatal head size below the population mean (K1.01 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 K1245 A-allele in contrast to G-allele carriers (PZ0.03). The association between the KG1245A SNP and head size remained significant after correction for birth weight and postnatal height SDS (PZ0.03). Birth weight, birth length and postnatal height SDS were not related with the -G1245A SNP. Conclusions: The K1245 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.

Growth and body composition in very young SGA children

“…Common IGF-I and IGF-IR gene polymorphisms have been investigated recently with negative results regarding postnatal growth impairment [15]. Ester et al [16] have shown that the -G1245A IGF-I polymorphism is associated with a small head and less brain sparing in children born SGA; however, more research is necessary in this area before definitive conclusions can be drawn.…”

IGF1 Promoter Polymorphism and Cranial Growth in Individuals Born Very Preterm

“…Previous studies have found associations between IGF1 promoter polymorphisms and birth weight, head circumference, stature, and IGF-1 level [2,3,5,6,9,11,12,30,31]. However, the direction of the reported associations varied considerably between these studies.…”

“…These measurements were expressed as SDS using Dutch reference values (corrected for prematurity until the age of 2 years) [18]. Brain sparing was defined as: head circumference SDS – length/height SDS [11]. …”

“…Associations between the two have been reported in children born small for gestational age [10,11] and in healthy newborns of diverse gestational ages [12]. However, these relations could not be replicated by other groups [5,6].…”

Regulation of IGFBP3 gene expression in short children born small for gestational age

“…The − 1245 G/A allele of the IGF1 promoter single nucleotide polymorphism (SNP) has been recently associated with a small head size and less brain sparing in SGA born subjects, particularly in those with the lowest birth weight [10]. Also the activity of the IGFBP1 is modulated by polymorphic variability and seems to be an additional player in the complex interaction between the IGF-IGFBP axis, glucose homeostasis and lipid metabolism [11].…”