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Effect of polyfluorinated compounds exposure and PPAR alpha pathway polymorphisms on maternal BMI and lipid profile, birth weight, growth and development of infants in Japan

多氟化合物暴露和 PPAR α 通路多态性对日本母亲 BMI 和血脂、出生体重、婴儿生长发育的影响

基本信息

批准号：
25893004
负责人：
GOUDARZI Houman
金额：
$ 1.66万
依托单位：
Hokkaido University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Research Activity Start-up
财政年份：
2013
资助国家：
日本
起止时间：
2013-08-30 至 2015-03-31
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-25893004/
关键词：
Prefluorinated chemicals PPAR Birth outcome Child growth

项目摘要

This study is a part of "The Hokkaido Study on Environment and Children's Health" as a prospective birth cohort. In this study, our objective is to evaluate the epidemiological effect of maternal PFCs exposure and peroxisome proliferator activating-receptors pathway polymorphisms on maternal lipid profile, birth outcome (birth weight, birth size), and children’s growth until school age.Prenatal levels of PFC compounds including PFOA and PFOS are available in maternal serum samples (n=514) between 2002 and 2005. Concentration of these chemicals were measured by liquid chromatography tandem mass spectrometry (LC-MS/MS). Primers for SNPs determination of following gens were purchased: PPARs (α, β, and γ), Leptin, LXR, HNF4α, and CAR. 400 μl of maternal whole blood samples which are collected immediately after delivery were subjected to the genomic DNA extraction. Using EP1 system (Fluidigm), I am examining SNP genotyping by end-point reading after PCR method. This process will be finished until 2014, September. After finishing genetic analysis, we assess the effect of prenatal PFCs exposure in underlying genetic background (SNPs in PPAR and PPAR-related pathways) on maternal TG and fatty acids during pregnancy. It may result in low birth size, and birth weight. Also, we are going to observe longitudinal effects of these chemical and genetic factors on child’s growth until school age. Therefore, we can identify of high risk groups classified by genetic susceptibility to PFCs exposure as a novel national pattern of environment-genetic interaction in Japanese population.

这项研究是《北海道环境与儿童健康研究》的一部分，是未来出生队列的一部分。在这项研究中，我们的目标是评估母亲PFC暴露和过氧化体增殖物激活受体途径多态对母亲血脂、出生结局(出生体重、出生大小)和儿童学龄前生长的流行病学影响。2002年至2005年期间，514名母亲的产前血清样本中存在PFC化合物水平，包括全氟辛酸和全氟辛酸。采用LC-MS/MS联用技术对这些化合物的浓度进行了测定。购买了PPAR(α，β和γ)、瘦素、LXR、HNF4α和CAR。对分娩后即刻采集的400例μ孕妇L的全血进行基因组提取。使用EP1系统(Fluidigm)，采用聚合酶链式反应(PCR)后的终点法进行SNP基因分型。这一进程将在2014年9月之前完成。在完成遗传分析后，我们评估了在潜在遗传背景(PPAR和PPAR相关途径中的SNPs)中产前PFC暴露对母亲孕期甘油三酯和脂肪酸的影响。这可能会导致低出生体型和出生体重。此外，我们还将观察这些化学和遗传因素对儿童生长发育的纵向影响，直到学龄。因此，我们可以确定根据PFC暴露遗传易感性分类的高危人群，这是日本人口环境-遗传交互作用的一种新的国家模式。