Association between insulin-like growth factor I (IGF-I) polymorphisms, circulating IGF-I, and pre- and postnatal growth in two European small for gestational age populations.

The purpose of this study was to assess the association of IGF-I and birth size by studying small for gestational age (SGA) subphenotypes and undertaking more detailed analysis of IGF-I genetic markers. SGA subjects from Haguenau, France (n = 113), and Gothenburg, Sweden (n = 174), were studied. The Swedish subjects were subphenotyped according to postnatal growth (114 short SGA and 60 SGA catch-up). IGF-I dinucleotide repeat and single nucleotide polymorphism (SNP) markers were studied, and haplotypes were generated in the Swedish short SGA group by identity of state. Association analysis was undertaken using the Monte Carlo method of association analysis of multiallelic markers for dinucleotide repeat markers, by exact chi(2) analysis for SNPs and by ANOVA for serum IGF-I levels. IGF-I genotype was associated with the SGA phenotype, in particular with symmetrical SGA and low birth weight, and with IGF-I levels in SGA subjects. Association with postnatal growth was different in the two populations, which may reflect the power of the smaller subphenotype groups. Haplotype analysis in the Swedish short SGA subjects showed that the region of association lay between the promoter and intron 2 of the IGF-I gene. These studies validate the association of the IGF-I gene with birth size and refine the region of association in Swedish short SGA subjects.