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

International Journal of Obesity volume 33, pages 962–970 (2009)Cite this article

Abstract

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.

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Acknowledgements

This work was financially supported by the Dutch Diabetes Research Foundation (DFN 2002.00.15) and the National Fund for Scientific Research Flanders (G.3.0269.97; G.0383.03). The EFPTS has been partly supported by grants from Funds of Scientific Research Flanders and by Twins, the Association for Scientific Research in Multiple Births Belgium. We are grateful to all the twins and their parents participating in this study. We thank Ingeborg Berckmoes, Annie Roossens, Lut De Zeure and Margaret Van Heuverswyn for fieldwork and technical assistance.

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Authors and Affiliations

  1. Department of Complex Genetics, Cluster of Genetics and Cell Biology, Maastricht University, Maastricht, The Netherlands

    N Y Souren, M Gielen & M P Zeegers

  2. Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, Maastricht, The Netherlands

    N Y Souren, A D C Paulussen, A Steyls, M Gielen & M P Zeegers

  3. Department of Public Health and Epidemiology, Unit of Genetic Epidemiology, University of Birmingham, Birmingham, UK

    N Y Souren, M Gielen & M P Zeegers

  4. Division of Clinical Genetics, Academic Hospital Maastricht, Maastricht, The Netherlands

    A D C Paulussen, A Steyls, R D Brandao, H J M Smeets & J P Geraedts

  5. Medical Research Council Epidemiology Unit, Cambridge, UK

    R J F Loos

  6. Department of Biomedical Kinesiology, Faculty of Kinesiology and Rehabilitation Sciences, Katholieke Universiteit Leuven, Leuven, Belgium

    R J F Loos & G Beunen

  7. Genome Center Maastricht, Maastricht University, Maastricht, The Netherlands

    H J M Smeets

  8. Department of Cardiovascular Diseases, Hypertension and Cardiovascular Rehabilitation Unit, Katholieke Universiteit Leuven, Leuven, Belgium

    R Fagard

  9. Department of Human Genetics, Katholieke Universiteit Leuven, Leuven, Belgium

    C Derom & R Vlietinck

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  1. N Y Souren
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Correspondence to N Y Souren.

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Supplementary Information accompanies the paper on International Journal of Obesity website (http://www.nature.com/ijo)

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Souren, N., Paulussen, A., Steyls, A. et al. Parent-of-origin specific linkage and association of the IGF2 gene region with birth weight and adult metabolic risk factors. Int J Obes 33, 962–970 (2009). https://doi.org/10.1038/ijo.2009.126

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