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

本研究是“北海道环境与儿童健康研究”的一部分，是一项前瞻性出生队列研究。在这项研究中，我们的目的是评估母体PFCs暴露和过氧化物酶体增殖物激活受体途径多态性对母体脂质谱、出生结局（出生体重、出生尺寸）和儿童生长直到学龄的流行病学影响。2002年至2005年期间，产妇血清样本（n=514）中含有产前PFC化合物水平，包括全氟辛酸和全氟辛烷磺酸。采用液相色谱串联质谱法（LC-MS/MS）测定了这些化学物质的浓度。购买了以下基因的snp检测引物：PPARs （α、β和γ）、Leptin、LXR、HNF4α和CAR。取分娩后立即采集的产妇全血400 μl进行基因组DNA提取。使用EP1系统（Fluidigm），我正在用PCR法后的终点读数检测SNP基因分型。这一过程将在2014年9月结束。在完成遗传分析后，我们评估了产前pfc暴露在潜在遗传背景（PPAR和PPAR相关通路的snp）对妊娠期间母体TG和脂肪酸的影响。它可能会导致出生时的小尺寸和体重。同时，我们将观察这些化学和遗传因素对儿童成长的纵向影响，直到入学年龄。因此，我们可以将PFCs暴露的遗传易感性分类为日本人群中环境-遗传相互作用的一种新的国家模式。

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.