title: Relation of FTO gene variants to fetal growth trajectories: Findings from the Southampton Women's survey.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: MRC Lifecourse Epidemiology Unit, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK. Electronic address: S.J.Barton@soton.ac.uk.
authors.forename: S J
authors.initials: SJ
authors.lastname: Barton
authors.affiliation: Institute of Developmental Sciences, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK; Department of Physiological Sciences, Faculty of Health, University of Valle, Cali, Colombia.
authors.forename: M
authors.initials: M
authors.lastname: Mosquera
authors.affiliation: Institute of Developmental Sciences, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK.
authors.forename: J K
authors.initials: JK
authors.lastname: Cleal
authors.affiliation: MRC Lifecourse Epidemiology Unit, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK.
authors.forename: A S
authors.initials: AS
authors.lastname: Fuller
authors.affiliation: MRC Lifecourse Epidemiology Unit, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK.
authors.forename: S R
authors.initials: SR
authors.lastname: Crozier
authors.affiliation: MRC Lifecourse Epidemiology Unit, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK; NIHR Musculoskeletal Biomedical Research Unit, University of Oxford, Oxford, OX1 2JD, UK.
authors.forename: C
authors.initials: C
authors.lastname: Cooper
authors.affiliation: MRC Lifecourse Epidemiology Unit, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK.
authors.forename: H M
authors.initials: HM
authors.lastname: Inskip
authors.affiliation: Human Genetics and Genomic Medicine, Human Development & Health, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK.
authors.forename: J W
authors.initials: JW
authors.lastname: Holloway
authors.affiliation: Institute of Developmental Sciences, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK.
authors.forename: R M
authors.initials: RM
authors.lastname: Lewis
authors.affiliation: MRC Lifecourse Epidemiology Unit, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK; NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, SO16 6YD, UK.
authors.forename: K M
authors.initials: KM
authors.lastname: Godfrey
mesh_terms: D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO / Q000235:genetics*; D001724:Birth Weight / Q000235:genetics; D002508:Cephalometry; D003430:Cross-Sectional Studies; D005260:Female; D047109:Fetal Development / Q000235:genetics*; D005333:Fetus / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009765:Obesity / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D012307:Risk Factors; D006113:United Kingdom
chemical_list: D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human
keywords: FTO genotype; Fetal growth trajectories; MC4R genotype; Placental FTO expression; Placental amino acid transporter expression