Relation of FTO gene variations to fetal growth trajectories: findings from the Southampton Women's survey
Relation of FTO gene variations to fetal growth trajectories: findings from the Southampton Women's survey
Introduction: Placental function is an important determinant of fetal growth, and fetal growth influences obesity risk in childhood and adult life. Here we investigated how FTO and MC4R gene variants linked with obesity relate to patterns of fetal growth and to placental FTO expression.
Methods: Southampton Women's Survey children (n = 1990) with measurements of fetal growth from 11 to 34 weeks gestation were genotyped for common gene variants in FTO (rs9939609, rs1421085) and MC4R (rs17782313). Linear mixed-effect models were used to analyse relations of gene variants with fetal growth.
Results: Fetuses with the rs9939609 A:A FTO genotype had faster biparietal diameter and head circumference growth velocities between 11 and 34 weeks gestation (by 0.012 (95% CI 0.005 to 0.019) and 0.008 (0.002–0.015) standard deviations per week, respectively) compared to fetuses with the T:T FTO genotype; abdominal circumference growth velocity did not differ between genotypes. FTO genotype was not associated with placental FTO expression, but higher placental FTO expression was independently associated with larger fetal size and higher placental ASCT2, EAAT2 and y + LAT2 amino acid transporter expression. Findings were similar for FTO rs1421085, and the MC4R gene variant was associated with the fetal growth velocity of head circumference.
Discussion: FTO gene variants are known to associate with obesity but this is the first time that the risk alleles and placental FTO expression have been linked with fetal growth trajectories. The lack of an association between FTO genotype and placental FTO expression adds to emerging evidence of complex biology underlying the association between FTO genotype and obesity.
fetal growth trajectories, FTO genotype, MC4R genotype, placental amino acid transporter expression, placental FTO expression
100-106
Barton, S.J.
4f674382-ca0b-44ad-9670-e71a0b134ef0
Mosquera, M.
2054c41f-762e-47a1-8865-db4adad1aa64
Cleal, J.K.
18cfd2c1-bd86-4a13-b38f-c321af56da66
Fuller, A.S.
0fd211bf-3719-496c-bbe5-a57d6d7fdc09
Crozier, S.R.
9c3595ce-45b0-44fa-8c4c-4c555e628a03
Cooper, C.
e05f5612-b493-4273-9b71-9e0ce32bdad6
Inskip, H.M.
5fb4470a-9379-49b2-a533-9da8e61058b7
Holloway, J.W.
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Lewis, R.M.
caaeb97d-ea69-4f7b-8adb-5fa25e2d3502
Godfrey, K.M.
0931701e-fe2c-44b5-8f0d-ec5c7477a6fd
February 2016
Barton, S.J.
4f674382-ca0b-44ad-9670-e71a0b134ef0
Mosquera, M.
2054c41f-762e-47a1-8865-db4adad1aa64
Cleal, J.K.
18cfd2c1-bd86-4a13-b38f-c321af56da66
Fuller, A.S.
0fd211bf-3719-496c-bbe5-a57d6d7fdc09
Crozier, S.R.
9c3595ce-45b0-44fa-8c4c-4c555e628a03
Cooper, C.
e05f5612-b493-4273-9b71-9e0ce32bdad6
Inskip, H.M.
5fb4470a-9379-49b2-a533-9da8e61058b7
Holloway, J.W.
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Lewis, R.M.
caaeb97d-ea69-4f7b-8adb-5fa25e2d3502
Godfrey, K.M.
0931701e-fe2c-44b5-8f0d-ec5c7477a6fd
Barton, S.J., Mosquera, M., Cleal, J.K., Fuller, A.S., Crozier, S.R., Cooper, C., Inskip, H.M., Holloway, J.W., Lewis, R.M. and Godfrey, K.M.
(2016)
Relation of FTO gene variations to fetal growth trajectories: findings from the Southampton Women's survey.
Placenta, 38, .
(doi:10.1016/j.placenta.2015.12.015).
Abstract
Introduction: Placental function is an important determinant of fetal growth, and fetal growth influences obesity risk in childhood and adult life. Here we investigated how FTO and MC4R gene variants linked with obesity relate to patterns of fetal growth and to placental FTO expression.
Methods: Southampton Women's Survey children (n = 1990) with measurements of fetal growth from 11 to 34 weeks gestation were genotyped for common gene variants in FTO (rs9939609, rs1421085) and MC4R (rs17782313). Linear mixed-effect models were used to analyse relations of gene variants with fetal growth.
Results: Fetuses with the rs9939609 A:A FTO genotype had faster biparietal diameter and head circumference growth velocities between 11 and 34 weeks gestation (by 0.012 (95% CI 0.005 to 0.019) and 0.008 (0.002–0.015) standard deviations per week, respectively) compared to fetuses with the T:T FTO genotype; abdominal circumference growth velocity did not differ between genotypes. FTO genotype was not associated with placental FTO expression, but higher placental FTO expression was independently associated with larger fetal size and higher placental ASCT2, EAAT2 and y + LAT2 amino acid transporter expression. Findings were similar for FTO rs1421085, and the MC4R gene variant was associated with the fetal growth velocity of head circumference.
Discussion: FTO gene variants are known to associate with obesity but this is the first time that the risk alleles and placental FTO expression have been linked with fetal growth trajectories. The lack of an association between FTO genotype and placental FTO expression adds to emerging evidence of complex biology underlying the association between FTO genotype and obesity.
Text
Bartonetal_Placenta_revised_nofieldcodes.docx
- Accepted Manuscript
Other
1-s2.0-S0143400415301119-main.pdf
- Version of Record
More information
Accepted/In Press date: 21 December 2015
e-pub ahead of print date: 24 December 2015
Published date: February 2016
Keywords:
fetal growth trajectories, FTO genotype, MC4R genotype, placental amino acid transporter expression, placental FTO expression
Organisations:
Faculty of Medicine
Identifiers
Local EPrints ID: 385162
URI: http://eprints.soton.ac.uk/id/eprint/385162
ISSN: 0143-4004
PURE UUID: 8e298f8c-c1f2-4b07-84e9-8b693f3adf5b
Catalogue record
Date deposited: 18 Jan 2016 09:57
Last modified: 18 Mar 2024 02:54
Export record
Altmetrics
Contributors
Author:
M. Mosquera
Author:
A.S. Fuller
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.
View more statistics
