Laboratory of Genetic Ecotoxicology, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
Environ Health Perspect. 2011 Feb;119(2):265-71. doi: 10.1289/ehp.1002470. Epub 2010 Oct 5.
Oxidative damage to placental DNA can result in negative pregnancy outcomes, including intrauterine growth restriction (IUGR) and low birth weight (LBW).
We investigated associations between the levels of 8-oxo-7,8-dihydro-2´-deoxyguanosine (8-oxodG), a marker of oxidative DNA damage, in placental DNA, exposure to air pollutants during pregnancy, genetic polymorphisms in 94 selected genes, and pregnancy outcomes.
We studied 891 newborns who were IUGR- or LBW-affected or normal weight and were born between 1994 and 1999 in the Czech Republic in two districts with different levels of air pollution.
We found nonsignificantly elevated 8-oxodG levels in the IUGR-affected group compared with the non-IUGR group (p = 0.055). Similarly, slightly elevated 8-oxodG levels were found in the LBW-affected group compared with the non-LBW group (p < 0.050). In univariate analyses, we identified single nucleotide polymorphisms associated with 8-oxodG levels, IUGR, and LBW. Exposure to particulate matter < 2.5 µm was associated with increased 8-oxodG levels in placental DNA and LBW. However, multivariate-adjusted logistic regression revealed that above-median 8-oxodG levels were the only factor significantly associated with IUGR [OR = 1.56; 95% confidence interval (CI), 1.07-2.37; p = 0.022]. Above-median levels of 8-oxodG were associated with LBW (OR = 1.88; 95% CI, 1.15-3.06; p = 0.011). Other variables associated with LBW included sex and gestational age of the newborn, maternal smoking, and haplotypes in the promoter region of the gene encoding mannose-binding lectin 2 (MBL2). The role of air pollutants in the risk of adverse pregnancy outcomes seemed to be less important.
Levels of 8-oxodG in placental DNA were associated with the risk of IUGR as well as LBW. Newborn's sex, gestational age, maternal smoking, and genetic polymorphisms in the promoter region of the MBL2 gene were associated with LBW incidence.
胎盘 DNA 的氧化损伤可导致妊娠结局不良,包括宫内生长受限(IUGR)和低出生体重(LBW)。
我们研究了胎盘 DNA 中 8-氧代-7,8-二氢-2'-脱氧鸟苷(8-oxodG)水平(氧化 DNA 损伤的标志物)与妊娠期间暴露于空气污染物、94 个选定基因中的遗传多态性之间的关系,以及与妊娠结局的关系。
我们研究了 1994 年至 1999 年期间在捷克共和国两个空气污染程度不同的地区出生的 891 名新生儿,他们或受到 IUGR 或 LBW 的影响,或体重正常。
与非 IUGR 组相比,IUGR 组的 8-oxodG 水平略有升高(p=0.055),但差异无统计学意义。同样,LBW 组的 8-oxodG 水平也略高于非 LBW 组(p<0.050)。在单变量分析中,我们发现了与 8-oxodG 水平、IUGR 和 LBW 相关的单核苷酸多态性。暴露于小于 2.5 µm 的颗粒物与胎盘 DNA 中 8-oxodG 水平升高和 LBW 有关。然而,多变量调整后的逻辑回归显示,中位数以上的 8-oxodG 水平是与 IUGR 显著相关的唯一因素[OR=1.56;95%置信区间(CI),1.07-2.37;p=0.022]。中位数以上的 8-oxodG 水平与 LBW 相关(OR=1.88;95%CI,1.15-3.06;p=0.011)。其他与 LBW 相关的变量包括新生儿的性别和胎龄、母亲吸烟以及甘露糖结合凝集素 2(MBL2)基因启动子区域的单倍型。空气污染物在不良妊娠结局风险中的作用似乎不那么重要。
胎盘 DNA 中 8-oxodG 水平与 IUGR 以及 LBW 的风险相关。新生儿的性别、胎龄、母亲吸烟以及 MBL2 基因启动子区域的遗传多态性与 LBW 的发生率相关。