Parent-of-origin specific linkage and association of the IGF2 gene region with birth weight and adult metabolic risk factors

Objective: The maternally imprinted insulin-like growth factor 2 (IGF2) gene is an important fetal growth factor and is also suggested to have postnatal metabolic effects. In this study, we examined whether common polymorphisms in IGF2 (6815_6819delAGGGC, 1156T>C and 820G>A (ApaI)) and a microsatellite marker in the close vicinity of IGF2 were linked to or associated with birth weight and adult metabolic risk factors. Design and participants: Polymorphisms were genotyped in 199 monozygotic complete twin pairs, 109 dizygotic complete twin pairs, 15 single twins, 231 mothers and 228 fathers recruited from the East Flanders Prospective Twin Survey. Conventional and parent-of-origin specific linkage and association analyses were carried out with birth weight, adult body height and parameters quantifying obesity, insulin sensitivity and dyslipidaemia measured at adult age (mean age 25 years). Results: In the parent-of-origin specific association analysis, in which only the paternally inherited allele was incorporated, the 1156T>C SNP (single nucleotide polymorphism) showed significant association with IGF-binding protein 1 (IGFBP1) levels (T and C (mean (95% CI)): 13.2 (12.1-14.3) and 16.2 (14.6-18.0) ng ml(-1), P = 0.002). No linkage was observed in either the conventional or in the parent-of-origin specific linkage analysis. Conclusion: This study suggests that paternally inherited alleles of a common polymorphism in the IGF2 gene affect IGFBP1 levels. International Journal of Obesity (2009) 33, 962-970; doi: 10.1038/ijo.2009.126; published online 23 June 2009