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

Division of Endocrinology, Department of Pediatrics, Erasmus MC/Sophia Children's Hospital, Rotterdam, The Netherlands¹ Department of Internal Medicine, Rotterdam, The Netherlands² Department of Epidemiology and Biostatistics, Erasmus MC, Rotterdam, The Netherlands

(Correspondence should be addressed to W A Ester who is now at Erasmus Medical Center, Ee2183, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands; Email: w.ester{at}erasmusmc.nl)

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.