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


CONCLUSIONS
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.
Key Laboratory of Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai 200032, China.
Changming
C
Xie
International Peace Maternity And Child Health Hospital, Shanghai, China.
Rong
R
Jin
Key Laboratory of Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai 200032, China.
Yan
Y
Zhao
Nantong Center for Disease and Control Prevention, Jiangsu, China.
Ling
L
Lin
Key Laboratory of Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai 200032, China.
Luxi
L
Li
Key Laboratory of Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai 200032, China.
Jiao
J
Chen
Key Laboratory of Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai 200032, China; The Innovation Center for Social Risk Governance in Health, School of Public Health, Fudan University, Shanghai 200032, China. Electronic address: yhzhang@shmu.edu.cn.
Yunhui
Y
Zhang
D043303:Aryldialkylphosphatase / Q000235:genetics*; D002681:China; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D018811:Maternal Exposure; D010795:Phthalic Acids / Q000633:toxicity*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011247:Pregnancy; D053719:Tandem Mass Spectrometry
D010795:Phthalic Acids; D043303:Aryldialkylphosphatase; C468411:PON2 protein, human
Birth length; Low birth weight; Modifying effect; PON2 A148G polymorphism; Phthalates