DNA甲基化在孕妇砷暴露与新生儿出生体重间的中介作用分析  

The mediation analysis of DNA methylation in the relationship between maternal arsenic exposure and neonatal birth weight

作　　者：房瑞玲 白文琳 崔跃华 王彤 FANG Ruiling;BAI Wenlin;CUI Yuehua;WANG Tong(Department of Health Statistics,School of Public Health,Shanxi Medical University,Taiyuan 030001,China;MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention,Shanxi Medical University,Taiyuan 030001,China;Department of Statistics and Probability,Michigan State University,East Lansing MI48824,USA)

机构地区：[1]山西医科大学公共卫生学院卫生统计学教研室,太原030001 [2]煤炭环境致病与防治教育部重点实验室,太原030001 [3]美国密西根州立大学统计与概率系,东兰辛MI48824

出　　处：《中华疾病控制杂志》2024年第9期1090-1095,共6页Chinese Journal of Disease Control & Prevention

基　　金：国家自然科学基金(82204164);山西省应用基础研究计划(20210302124409);中国博士后科学基金(2021M691990)。

摘　　要：目的探讨DNA甲基化(DNA methylation,DNAm)水平的改变是否在孕期砷暴露与新生儿出生体重之间有中介作用。方法资料来自新罕布什尔州出生队列研究,研究对象为2012年2月―2013年9月入选该队列的343对母婴,数据可从高通量基因表达(gene expression omnibus,GEO)数据库获取,检索号为GSE71678,共有270对母婴纳入本研究。采用确定独立筛选(sure independence screening,SIS)策略和中介效应分析方法估计DNAm位点在胎盘砷暴露与出生体重之间的中介效应。结果调整孕妇年龄、孕前BMI、妊娠期糖尿病、胎龄、新生儿性别、胎盘组织细胞成分后,筛选出25个候选中介DNAm位点。中介效应分析结果显示,通过Bonferroni法校正后,识别出位于VENTX基因上的cg14900295在孕期砷暴露致低出生体重有中间的作用(ACME=0.0576,95%CI:0.0176~0.1064,P=0.0008);通过FDR方法校正,识别出18个胞嘧啶-磷酸-鸟嘌呤双核苷酸(cytosine-phosphate-guanine pairs of nucleotides,CpG)位点有中介作用,其中cg03348978、cg02435495、cg09463047、cg11862993均位于HNF1B基因。结论在妊娠期砷暴露导致低出生体重的过程中,共有18个特异性位点的DNAm水平改变起到了重要的中介作用,VENTX和HNF1B基因可能是其病因机制中的关键环节,为揭示砷暴露致低出生体重的遗传病因机制提供了参考依据。Objective To investigate whether the changes of DNA methylation level mediate the relationship between prenatal arsenic exposure and neonatal birth weight.Methods Data of this study were derived from the New Hampshire Birth Cohort Study,with 343 mother-infant pairs enrolled in the cohort from February 2012 to September 2013 and available from the GEO database under accession number GSE71678.A total of 270 maternal and infant pairs were included in this study.The Sure independence screening(SIS)strategy and mediation analysis method were employed to estimate the mediation effect of DNA methylation sites between placental arsenic exposure and birth weight.Results After adjusting for maternal age,pre-pregnancy BMI,gestational diabetes mellitus,gestational age,infant gender,and placental tissue cell composition,25 DNA methylation sites were selected as candidate mediators.The results of mediation analysis showed that after corrected by Bonferroni method.cg14900295 located on the VENTX gene was identified as a mediator between maternal arsenic exposure and low birth weight(ACME=0.0576,95%CI:0.0176-0.1064,P=0.0008).After corrected by FDR method,18 CpG loci were identified as mediators,among which cg03348978,cg02435495,cg09463047 and cg11862993 were all located on the HNF1B gene.Conclusions This study identified 18 specific sites where changes in DNA methylation levels play a crucial mediating role in the process linking prenatal arsenic exposure to low birth weight.Genes VENTX and HNF1B may be the key factors in the etiological mechanism.Therefore,these findings can provide a reference for revealing the genetic etiology mechanism of arsenic-induced low birth weight.

关 键 词：DNA甲基化 孕妇砷暴露 出生体重 中介效应 

分 类 号：R181.3[医药卫生—流行病学] R174[医药卫生—公共卫生与预防医学]