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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
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
0143-4004
100-106
Barton, S.J.
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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.
a97b1967-f6af-413a-8eb0-69fa25534d68
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.
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.
a97b1967-f6af-413a-8eb0-69fa25534d68
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, 100-106. (doi:10.1016/j.placenta.2015.12.015).

Record type: Article

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.

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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
ORCID for S.J. Barton: ORCID iD orcid.org/0000-0003-4963-4242
ORCID for J.K. Cleal: ORCID iD orcid.org/0000-0001-7978-4327
ORCID for C. Cooper: ORCID iD orcid.org/0000-0003-3510-0709
ORCID for H.M. Inskip: ORCID iD orcid.org/0000-0001-8897-1749
ORCID for J.W. Holloway: ORCID iD orcid.org/0000-0001-9998-0464
ORCID for R.M. Lewis: ORCID iD orcid.org/0000-0003-4044-9104
ORCID for K.M. Godfrey: ORCID iD orcid.org/0000-0002-4643-0618

Catalogue record

Date deposited: 18 Jan 2016 09:57
Last modified: 03 Dec 2019 02:04

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Contributors

Author: S.J. Barton ORCID iD
Author: M. Mosquera
Author: J.K. Cleal ORCID iD
Author: A.S. Fuller
Author: S.R. Crozier
Author: C. Cooper ORCID iD
Author: H.M. Inskip ORCID iD
Author: J.W. Holloway ORCID iD
Author: R.M. Lewis ORCID iD
Author: K.M. Godfrey ORCID iD

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