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中国新生儿对氧磷酶2基因多态性与产前邻苯二甲酸盐暴露情况

Paraoxonase 2 gene polymorphisms and prenatal phthalates' exposure in Chinese newborns.

作者信息

Xie Changming, Jin Rong, Zhao Yan, Lin Ling, Li Luxi, Chen Jiao, Zhang Yunhui

机构信息

Key Laboratory of Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai 200032, China.

International Peace Maternity And Child Health Hospital, Shanghai, China.

出版信息

Environ Res. 2015 Jul;140:354-9. doi: 10.1016/j.envres.2015.03.028. Epub 2015 Apr 24.

Abstract

BACKGROUND

Phthalates were reported to be associated with increased risk of LBW in newborns, but the mechanism and potential influencing factor was still unclear. The objectives of this study were to investigate whether paraoxonase-2 (PON2) Ala148Gly (A148G) polymorphisms have impacts on fetal growth, and evaluate potential modifying effect on the association between phthalate exposures and LBW and short birth length.

METHODS

In the current case-control study, 185 mother-newborn pairs including 74 low birth weight (LBW) cases and 111 controls were enrolled. Newborns' meconium specimens were collected and detected for mono-n-butyl phthalate (MBP) and mono-2-ethyhexyl phthalate (MEHP) by the method of high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). Umbilical vein blood samples were used to identify PON2 A148G polymorphisms by using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.

RESULTS

Newborns prenatally exposed to higher level of phthalates had lower birth weight (β=-0.92. p=0.045 for MBP, β=-0.62, p=0.013 for MEHP) and short birth length (SBL) (β=-0.024. p=0.049 for MBP, β=-0.023, p=0.007 for MEHP). Comparing with low-phthalate-exposed subjects with PON2 148AA genotype, newborns with PON2 148AG/GG genotype exposed to high concentrations of MBP and MEHP had higher risks of LBW and short birth length (LBW: OR: 5.0, p=0.017 for MEHP; OR: 2.6, p=0.023 for MBP; SBL: OR: 6.6, p=0.005 for MEHP; OR: 6.4, p=0.017 for MBP). Effects of MBP and MEHP on LBW were significantly modified by PON2 A148G (p=0.044 and 0.034, respectively), while the modifying effect of PON2 A148G polymorphisms on the association of two phthalate metabolites with SBL was not significant.

CONCLUSION

Prenatal exposure to phthalates affected birth weight and length in newborns. PON2 A148G polymorphisms modified the effects of prenatal phthalates' exposure on fetal development. Newborns with PON2 148AG/GG genotype and exposed to high concentrations of MBP and MEHP had higher risks of LBW and SBL.

摘要

背景

有报道称邻苯二甲酸盐与新生儿低出生体重风险增加有关,但其机制和潜在影响因素仍不清楚。本研究的目的是调查对氧磷酶-2(PON2)Ala148Gly(A148G)基因多态性是否对胎儿生长有影响,并评估其对邻苯二甲酸盐暴露与低出生体重和出生身长缩短之间关联的潜在修饰作用。

方法

在当前的病例对照研究中,纳入了185对母婴,其中包括74例低出生体重(LBW)病例和111例对照。收集新生儿胎粪标本,采用高效液相色谱-串联质谱法(LC-MS/MS)检测其中的邻苯二甲酸单丁酯(MBP)和邻苯二甲酸单(2-乙基己基)酯(MEHP)。采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法,利用脐静脉血样本鉴定PON2 A148G基因多态性。

结果

产前暴露于较高水平邻苯二甲酸盐的新生儿出生体重较低(MBP的β=-0.92,p=0.045;MEHP的β=-0.62,p=0.013),出生身长较短(SBL)(MBP的β=-0.024,p=0.049;MEHP的β=-0.023,p=0.007)。与PON2 148AA基因型且邻苯二甲酸盐暴露水平低的受试者相比,PON2 148AG/GG基因型且暴露于高浓度MBP和MEHP的新生儿发生低出生体重和出生身长缩短的风险更高(低出生体重:MEHP的OR:5.0,p=0.017;MBP的OR:2.6,p=0.023;出生身长缩短:MEHP的OR:6.6,p=0.005;MBP的OR:6.4,p=0.017)。PON2 A148G对MBP和MEHP导致低出生体重的影响有显著修饰作用(p分别为0.044和0.034),而PON2 A148G基因多态性对两种邻苯二甲酸酯代谢物与出生身长缩短之间关联的修饰作用不显著。

结论

产前暴露于邻苯二甲酸盐会影响新生儿的出生体重和身长。PON2 A148G基因多态性修饰了产前邻苯二甲酸盐暴露对胎儿发育的影响。PON2 148AG/GG基因型且暴露于高浓度MBP和MEHP的新生儿发生低出生体重和出生身长缩短的风险更高。

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