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Relation of FTO gene variants 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: Sou...

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Autores principales: 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., Godfrey, K.M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4776702/
https://www.ncbi.nlm.nih.gov/pubmed/26907388
http://dx.doi.org/10.1016/j.placenta.2015.12.015
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author 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.
Godfrey, K.M.
author_facet 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.
Godfrey, K.M.
author_sort Barton, S.J.
collection PubMed
description 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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spelling pubmed-47767022016-03-15 Relation of FTO gene variants to fetal growth trajectories: Findings from the Southampton Women's survey 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. Godfrey, K.M. Placenta Article 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. Elsevier 2016-02 /pmc/articles/PMC4776702/ /pubmed/26907388 http://dx.doi.org/10.1016/j.placenta.2015.12.015 Text en © 2016 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
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.
Godfrey, K.M.
Relation of FTO gene variants to fetal growth trajectories: Findings from the Southampton Women's survey
title Relation of FTO gene variants to fetal growth trajectories: Findings from the Southampton Women's survey
title_full Relation of FTO gene variants to fetal growth trajectories: Findings from the Southampton Women's survey
title_fullStr Relation of FTO gene variants to fetal growth trajectories: Findings from the Southampton Women's survey
title_full_unstemmed Relation of FTO gene variants to fetal growth trajectories: Findings from the Southampton Women's survey
title_short Relation of FTO gene variants to fetal growth trajectories: Findings from the Southampton Women's survey
title_sort relation of fto gene variants to fetal growth trajectories: findings from the southampton women's survey
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4776702/
https://www.ncbi.nlm.nih.gov/pubmed/26907388
http://dx.doi.org/10.1016/j.placenta.2015.12.015
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