孕妇基因多态性和自发性早产发生风险的关联性研究

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摘要目的研究8种代谢酶基因单核苷酸多态性(SNPs)以及PM_2.5环境污染物与自发性早产发生是否存在关联。方法采用病例对照研究,以2013年3月至2014年12月在北京市海淀区妇幼保健院分娩自发性早产儿的孕妇作为病例组,以同院分娩健康足月儿的孕妇作为对照组。共募集到孕妇308例,排除实验数据缺失者,最终有306例孕妇进入本次研究,其中病例组103例,对照组203例。收集孕妇的基本信息和妊娠情况,同时采集孕妇静脉血测定基因型。以美国国务院公布北京市2013—2014年度每日PM_2.5数据作为环境PM_2.5暴露资料,采用盐析法提取白细胞DNA,基质支持的激光释放/电离飞行时间质谱(MALDA-TOF MS)检测,分析基因和环境污染对自发性早产的影响。结果病例组和对照组在一般人口学特征和妊娠情况上差异均无统计学意义,两组孕妇在PM_2.5暴露程度上差异无统计学意义。参与编码CYP1A2的rs2472304在两组间的基因频率和基因型频率的差异均有统计学意义,Logistic回归发现显性遗传模式下的rs2472304的突变基因型(AA/GA)相较于野生型基因(GG)对早产的发生有保护作用(OR=0.52,95% CI:0.30～0.90)。PM_2.5暴露浓度分层分析显示,突变基因型在高浓度暴露时对自发性早产有保护作用。结论 rs2472304的突变与自发性早产的发生有关,未发现环境PM_2.5暴露与自发性早产的发生存在关联。

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	庞一鸣
	王佳楣
	刘念
	陈小兰
	刘晓红
	王斌
	李智文

关键词 ：自发性早产, 单核苷酸多态性, SNPs, PM_2.5

Abstract：Objective To study the association between spontaneous preterm birth (SPB) and its potential risk factors including single nucleotide polymorphism (SNP) of metabolism enzyme and the ambient exposure to PM_2.5. Methods A case-control study was conducted based on the patients in the Haidian District Maternal and Child Health Hospital from March 2013 to December 2014. The cases were SPB women, and mothers with term delivery acted as controls. Population characteristics, pregnancy information and venous blood were also collected. The ambient concentrations of PM_2.5 were obtained from U.S. embassy monitor in Beijing. DNA was extracted by salt-out method and genotyped by Matrix assisted laser desorption ionization/time of flight mass spectrometry (MALDA-TOF MS). Statistics of the between-group comparison were calculated to explore the risk factors of SPB. Results Population characteristics and pregnancy conditions were similar between the case and control group (P>0.05). The exposure level of PM_2.5 was similar, as well (P>0.05). Either allele or genotype frequency of rs2472304, a SNP of CYP1A2 was significantly different between the case and control group (P<0.001). Based on the results of the logistic regression, we found the mutant genotype of rs2472304 (AA/GA) had a protective effect on SPB, compared to the wild genotype (GG). Based on the model on the interaction between PM_2.5 exposure and the SNP, the protective effect of the mutant genotype was stronger under more polluted scenario. Conclusion The mutation of rs2472304 was associated with SPB. We didn’t found a significant association between PM_2.5 exposure and SPB.

Key words： spontaneous preterm birth single nucleotide polymorphism SNPs PM_2.5

收稿日期: 2019-01-15

通讯作者: 李智文(lizw@bjmu.edu.cn)

引用本文:

庞一鸣, 王佳楣, 刘念, 陈小兰, 刘晓红, 王斌, 李智文. 孕妇基因多态性和自发性早产发生风险的关联性研究[J]. 中国生育健康杂志, 2020, 31(2): 132-136.
PANG Yiming, WANG Jiamei, LIU Nian, CHEN Xiaolan, LIU Xiaohong, WANG Bin, LI Zhiwen. Association between risk of spontaneous preterm birth and single nucleotide polymorphism. Chinese Journal of Reproductive Health, 2020, 31(2): 132-136.

链接本文:

http://cjrh.bjmu.edu.cn/CN/ 或 http://cjrh.bjmu.edu.cn/CN/Y2020/V31/I2/132

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