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Polymorphisms in genes within the IGF-axis influence antenatal and postnatal growth

Published online by Cambridge University Press:  24 October 2012

P. G. Parmar ,
J. A. Marsh ,
H. Rob Taal ,
M. Kowgier ,
A. G. Uitterlinden ,
F. Rivadeneira ,
L. Briollais ,
J. P. Newnham ,
A. Hofman  and
S. J. Lye
...Show all authors
P. G. Parmar
Affiliation:
School of Women's and Infants’ Health, The University of Western Australia, Perth, WA, Australia
J. A. Marsh
Affiliation:
School of Women's and Infants’ Health, The University of Western Australia, Perth, WA, Australia
H. Rob Taal
Affiliation:
The Generation R Study Group, Erasmus Medical Center, Rotterdam, The Netherlands Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands Department of Pediatrics, Erasmus Medical Center, Rotterdam, The Netherlands
M. Kowgier
Affiliation:
Samuel Lunenfeld Research Institute, University of Toronto, Ontario, Canada Ontario Institute for Cancer Research, University of Toronto, Ontario, Canada
A. G. Uitterlinden
Affiliation:
Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
F. Rivadeneira
Affiliation:
Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
L. Briollais
Affiliation:
Samuel Lunenfeld Research Institute, University of Toronto, Ontario, Canada
J. P. Newnham
Affiliation:
School of Women's and Infants’ Health, The University of Western Australia, Perth, WA, Australia
A. Hofman
Affiliation:
Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands
S. J. Lye
Affiliation:
Samuel Lunenfeld Research Institute, University of Toronto, Ontario, Canada
E. A. P. Steegers
Affiliation:
Department of Obstetrics Gynecology, Erasmus Medical Center, Rotterdam, The Netherlands
C. M. van Duijn
Affiliation:
Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands
L. J. Palmer
Affiliation:
Samuel Lunenfeld Research Institute, University of Toronto, Ontario, Canada Ontario Institute for Cancer Research, University of Toronto, Ontario, Canada
V. W. V. Jaddoe
Affiliation:
The Generation R Study Group, Erasmus Medical Center, Rotterdam, The Netherlands Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands Department of Pediatrics, Erasmus Medical Center, Rotterdam, The Netherlands
C. E. Pennell*
Affiliation:
School of Women's and Infants’ Health, The University of Western Australia, Perth, WA, Australia
*
*Address for correspondence: C. E. Pennell, MBBS, PhD, School of Women's and Infants' Health, The University of Western Australia, 35 Stirling Hwy, Crawley WA 6009 Australia, UWA Mail Box: M550. (Email cpennell@meddent.uwa.edu.au)
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Abstract

Two pregnancy cohorts were used to investigate the association between single-nucleotide polymorphisms (SNPs) in genes within the insulin-like growth factor (IGF)-axis and antenatal and postnatal growth from birth to adolescence. Longitudinal analyses were conducted in the Raine pregnancy cohort (n = 1162) using repeated measures of fetal head circumference (HC), abdominal circumference (AC) and femur length (FL) from 18 to 38 weeks gestation and eight measures of postnatal height and weight (1–17 years). Replications of significant associations up to birth were undertaken in the Generation R Study (n = 2642). Of the SNPs within the IGF-axis genes, 40% (n = 58) were associated with measures of antenatal growth (P ⩽ 0.05). The majority of these SNPs were in receptors; IGF-1R (23%; n = 34) and IGF-2R (13%; n = 9). Fifteen SNPs were associated with antenatal growth (either AC or HC or FL) in Raine (P ⩽ 0.005): five of which remained significant after adjusting for multiple testing. Four of these replicated in Generation R. Associations were identified between 38% (n = 55) of the IGF-axis SNPs and postnatal height and weight; 21% in IGF-1R (n = 31) and 9% in IGF-2R (n = 13). Twenty-six SNPs were significantly associated with both antenatal and postnatal growth; 17 with discordant effects and nine with concordant effects. Genetic variants in the IGF-axis appear to play a significant role in antenatal and postnatal growth. Further replication and new analytic methods are required in order to better understand this key metabolic pathway integrating biologic knowledge about the interaction between IGF-axis components.

Keywords

developmental growthDOHaDIGFinsulin-like growth factor pathwayRaine studySNP
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 4 , Issue 2 , April 2013 , pp. 157 - 169
Copyright
Copyright © Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2012 

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