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
MRC Lifecourse Epidemiology Unit, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK.
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.
Placenta. 2016 Feb;38:100-6. doi: 10.1016/j.placenta.2015.12.015. Epub 2015 Dec 24.
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.
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.
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.
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.
胎盘功能是胎儿生长的重要决定因素，而胎儿生长会影响儿童期和成年期的肥胖风险。在此，我们研究了与肥胖相关的FTO和MC4R基因变异如何与胎儿生长模式以及胎盘FTO表达相关。
对南安普顿妇女调查中的儿童（n = 1990）进行基因分型，这些儿童在妊娠11至34周时有胎儿生长测量数据，检测FTO（rs9939609、rs1421085）和MC4R（rs17782313）的常见基因变异。使用线性混合效应模型分析基因变异与胎儿生长的关系。
与FTO基因型为T:T的胎儿相比，基因型为A:A的rs9939609 FTO胎儿在妊娠11至34周时双顶径和头围生长速度更快（分别为每周0.012（95%可信区间0.005至0.019）和0.008（0.002 - 0.015）标准差）；不同基因型间腹围生长速度无差异。FTO基因型与胎盘FTO表达无关，但较高的胎盘FTO表达与较大的胎儿大小以及较高的胎盘ASCT2、EAAT2和y + LAT2氨基酸转运体表达独立相关。FTO rs1421085的结果相似，且MC4R基因变异与头围的胎儿生长速度相关。
已知FTO基因变异与肥胖有关，但这是首次将风险等位基因和胎盘FTO表达与胎儿生长轨迹联系起来。FTO基因型与胎盘FTO表达之间缺乏关联，这进一步证明了FTO基因型与肥胖之间关联背后复杂生物学机制的新证据。
