Introduction

Particulate air pollution is probably causally related to increased risk of cardiovascular disease. Plasma homocysteine is an established cardiovascular disease risk factor. Recent studies show that exposure to particulate air pollution is associated with plasma homocysteine levels in adults but no studies on the association between prenatal air pollution and neonatal homocysteine levels exist.

Methods

In 609 newborns of the ENVIRONAGE (ENVIRonmental influence ON early AGEing) birth cohort, we investigated the association between prenatal particulate matter exposure with a diameter ≤ 2.5 µm (PM_2.5) and cord plasma homocysteine levels, and in a subset (n = 490) we studied the interaction with 11 single nucleotide polymorphism (SNPs) in oxidative stress-related genes (CAT, COMT, GSTP1, SOD2, NQO1 and HFE), through multiple linear regression. PM_2.5 levels were obtained using a high resolution spatial temporal interpolation method. Homocysteine levels were measured by the homocysteine enzymatic assay on a Roche/Hitachi cobas c system. SNPs were assessed on the Biotrove OpenArray SNP genotyping platform.

Results

In multivariable-adjusted models, cord plasma homocysteine levels were 8.1% higher (95% CI: 1.9 to 14.3%; p = 0.01) for each 5 µg/m³ increment in average PM_2.5 exposure during the entire pregnancy. With regard to pregnancy trimesters, there was only an association in the 2^nd trimester: 3.6% (95% CI: 0.9% to 6.4%; p = 0.01). The positive association between PM_2.5 in and homocysteine was (borderline) statistically significantly modified by genetic variants in MnSOD (p interaction = 0.02), GSTP1 (p interaction = 0.07) and the sum score of the 3 studied SNPs in the CAT gene (p interaction=0.09), suggesting oxidative stress as an underlying mechanism of action.

Conclusions

Exposure to particulate air pollution in utero is associated with higher cord blood homocysteine levels, possibly through generating oxidative stress. Increased air pollution-induced homocysteine levels in early life might predispose for cardiovascular and other diseases later in life.

中文翻译：

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新生儿的产前颗粒物空气污染暴露和脐带血同型半胱氨酸：ENVIR ON AGE出生队列的结果

介绍

空气中的颗粒物污染可能与心血管疾病的风险增加有因果关系。血浆同型半胱氨酸是已确定的心血管疾病危险因素。最近的研究表明，暴露于颗粒空气污染与成年人血浆同型半胱氨酸水平有关，但尚无关于产前空气污染与新生儿同型半胱氨酸水平之间关系的研究。

方法

在ENVIR 609个新生儿ON AGE（环境影响ON早期老化）出生队列中，我们调查产前颗粒物曝光，其直径≤2.5微米（PM之间的关联_2.5）和帘线血浆同型半胱氨酸水平，并且在一个子集（N = 490），我们通过多元线性回归研究了氧化应激相关基因（CAT，COMT，GSTP1，SOD2，NQO1和HFE）中11个单核苷酸多态性（SNP）的相互作用。下午_2.5使用高分辨率的空间时间插值方法获得水平。通过在Roche / Hitachi cobas c系统上的同型半胱氨酸酶促测定法测量同型半胱氨酸水平。在Biotrove OpenArray SNP基因分型平台上评估了SNP。

结果

在多变量调整模型中，整个怀孕期间平均PM _2.5暴露每增加5 µg /m³，脐带血浆同型半胱氨酸水平就会增加8.1％（95％CI：1.9至14.3％； p = 0.01）。对于妊娠三个月，只有在2关联^第二三个月：3.6％（95％CI：0.9％至6.4％; P = 0.01）。MnSOD（p相互作用= 0.02），GSTP1（p相互作用= 0.07）和CAT基因中3个研究的SNPs的总得分在统计学上显着修饰了PM _2.5与高半胱氨酸之间的正相关（边界）。相互作用= 0.09），表明氧化应激是一种潜在的作用机理。

结论

子宫中暴露于颗粒空气污染与脐带血同型半胱氨酸水平升高有关，可能是通过产生氧化应激引起的。生命早期增加的空气污染诱导的同型半胱氨酸水平可能会导致生命后期的心血管疾病和其他疾病。