Krishnan Mohanraj, Thompson John M D, Mitchell Edwin A, Murphy Rinki, McCowan Lesley M E, Shelling Andrew N, On Behalf Of The Children Of Scope Study Group G
Department of Obstetrics and Gynaecology, University of Auckland, New Zealand.
Department of Paediatrics: Child & Youth Health, University of Auckland, New Zealand.
Mol Biosyst. 2017 Jul 25;13(8):1524-1533. doi: 10.1039/c7mb00104e.
Childhood obesity is a public health problem, which is associated with a long-term increased risk of cardiovascular disease and premature mortality. Several gene variants have previously been identified that have provided novel insights into biological factors that contribute to the development of obesity. As obesity tracks through childhood into adulthood, identification of the genetic factors for obesity in early life is important. The objective of this study was to identify putative associations between genetic variants and obesity traits in children at 6 years of age. We recruited 1208 children of mothers from the New Zealand centre of the international Screening for Pregnancy Endpoints (SCOPE) study. Eighty common genetic variants associated with obesity traits were evaluated by the Sequenom assay. Body mass index standardised scores (BMI z-scores) and percentage body fat (PBF; measured by bio-impedance assay (BIA)) were used as anthropometric measures of obesity. A positive correlation was found between BMI z-scores and PBF (p < 0.001, r = 0.756). Two subsets of gene variants were associated with BMI z-scores (HOXB5-rs9299, SH2B1-rs7498665, NPC1-rs1805081 and MSRA-rs545854) and PBF (TMEM18-rs6548238, NPY-rs17149106, ETV-rs7647305, NPY-rs16139, TIMELESS-rs4630333, FTO-rs9939609, UCP2-rs659366, MAP2K5-rs2241423 and FAIM2-rs7138803) in the genotype models. However, there was an absence of overlapping association between any of the gene variants with BMI z-scores and PBF. A further five variants were associated with BMI z-scores (TMEM18-rs6548238, FTO-rs9939609 and MC4R-rs17782313) and PBF (SH2B1-rs7498665 and FTO-rs1421085) once separated by genetic models (additive, recessive and dominant) of inheritance. This study has identified significant associations between numerous gene variants selected on the basis of prior association with obesity and obesity traits in New Zealand European children.
儿童肥胖是一个公共卫生问题，与心血管疾病风险长期增加及过早死亡相关。此前已鉴定出若干基因变异，这些变异为导致肥胖发生的生物学因素提供了新见解。由于肥胖会从儿童期持续到成年期，因此确定生命早期肥胖的遗传因素很重要。本研究的目的是确定6岁儿童基因变异与肥胖特征之间的假定关联。我们从国际孕期终点筛查（SCOPE）研究的新西兰中心招募了1208名母亲的子女。通过Sequenom检测评估了80个与肥胖特征相关的常见基因变异。体重指数标准化分数（BMI z评分）和体脂百分比（PBF；通过生物电阻抗分析（BIA）测量）被用作肥胖的人体测量指标。发现BMI z评分与PBF之间存在正相关（p < 0.001，r = 0.756）。在基因型模型中，两组基因变异分别与BMI z评分（HOXB5-rs9299、SH2B1-rs7498665、NPC1-rs1805081和MSRA-rs545854）及PBF（TMEM18-rs6548238、NPY-rs17149106、ETV-rs7647305、NPY-rs16139、TIMELESS-rs4630333、FTO-rs9939609、UCP2-rs659366、MAP2K5-rs2241423和FAIM2-rs7138803）相关。然而，在任何与BMI z评分和PBF相关的基因变异之间均未发现重叠关联。一旦按遗传模型（加性、隐性和显性）进行遗传分离，另外五个变异与BMI z评分（TMEM18-rs6548238、FTO-rs9939609和MC4R-rs17782313）及PBF（SH2B1-rs7498665和FTO-rs1421085）相关。本研究确定了基于先前与肥胖的关联而选择的众多基因变异与新西兰欧洲儿童肥胖特征之间的显著关联。
