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Fat mass and obesity-associated obesity-risk genotype is associated with lower foetal growth: an effect that is reversed in the offspring of smoking mothers

Published online by Cambridge University Press:  26 October 2011

J. A. Marsh*
Affiliation:
Centre for Genetic Epidemiology and Biostatistics, The University of Western Australia, Perth, Australia
C. E. Pennell
Affiliation:
School of Women's and Infants’ Health, The University of Western Australia, Perth, Australia
N. M. Warrington
Affiliation:
Centre for Genetic Epidemiology and Biostatistics, The University of Western Australia, Perth, Australia
D. Mook-Kanamori
Affiliation:
Department of Epidemiology, Erasmus Medical Centre, Rotterdam, the Netherlands
L. Briollais
Affiliation:
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
S. J. Lye
Affiliation:
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
L. J. Beilin
Affiliation:
School of Medicine and Pharmacology, The University of Western Australia, Perth, Australia
E. Steegers
Affiliation:
Department of Epidemiology, Erasmus Medical Centre, Rotterdam, the Netherlands
A. Hofman
Affiliation:
Department of Epidemiology, Erasmus Medical Centre, Rotterdam, the Netherlands
V. W. V. Jaddoe
Affiliation:
Department of Epidemiology, Erasmus Medical Centre, Rotterdam, the Netherlands
J. P. Newnham
Affiliation:
School of Women's and Infants’ Health, The University of Western Australia, Perth, Australia
L. J. Palmer
Affiliation:
Centre for Genetic Epidemiology and Biostatistics, The University of Western Australia, Perth, Australia
*
*Address for correspondence: J. A. Marsh, Centre for Genetic Epidemiology and Biostatistics, University of Western Australia M409, 35 Stirling Highway, Crawley, WA 6009, Australia.(Email marshj02@student.uwa.edu.au)

Abstract

Fat mass and obesity-associated (FTO) gene variants are associated with childhood and adult obesity; however, the influence of FTO polymorphisms on foetal growth is unknown. Associations between the FTO variant rs9939609 and the foetal growth trajectories, maternal pregnancy weight gain, anthropometric measures at birth and body mass index (BMI) at age 14 years were assessed in 1079 singleton-birth Australian Caucasians. Analyses were repeated in 3512 singleton-birth Dutch Caucasians. The rs9939609 obesity-risk AA genotype was associated with symmetrical intrauterine growth restriction; an effect reversed in mothers who smoked during pregnancy. The effect increased over time and was modified by maternal smoking for head circumference (P = 0.007), abdominal circumference (P = 0.007), femur length (P = 0.02) and estimated foetal weight (P = 0.001). The modification of the association between the AA genotype and birth anthropometrics by maternal smoking was consistent across birth weight (P = 0.01) and birth length (P = 0.04) and neonatal day 2 anthropometry. Consistent associations were replicated in the Generation R cohort. Maternal pregnancy weight gain matched the pattern of birth weight and was independent of placental weight. In adolescents, the AA genotype was associated with increased BMI-adjusted-for-age in males (P = 0.00009), but no effect was detected in females. A variant in the FTO gene influences foetal growth trajectories in the third trimester, early postnatal growth and adiposity in adolescence. Maternal smoking during pregnancy reversed the direction of association of rs9939609 on foetal growth, which was probably mediated by maternal energy intake. The detection of genetic variants associated with foetal growth has the potential to identify novel molecular mechanisms underlying growth and targeted early life intervention.

Type
Original Articles
Copyright
Copyright © Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2011

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