Abstract：
BACKGROUND: Use of Methamphetamine during pregnancy is significant public health concern since it affects the development of the brain and poor behavioral outcomes in children. Prenatal methamphetamine exposure (PME) may cause developmental disabilities and several gene expression and molecular pathways alterations. In the present study, DNA methylation of Propionyl-CoA Carboxylase subunit Beta (PCCB) and Protocadherin Alpha 12 (PCDHA12) genes were assessed in two groups of three-year-old children, those exposed to PME and healthy control children.
OBJECTIVE: Clarification of PME role in methylation level of two mitochondria function associated genes; PCCB and PCDHA12.
METHODS: In this study, 2629 children with PME (1531male, 1098 female) and 3523(2077male, 1446 female) control children were recruited based on maternal self-report of prenatal exposure. Genomic DNA extracted from peripheral blood and pyrosequencing was used to determine the association between prenatal MA exposure and methylation in nine CpG sites of PCCB and PCDHA12 genes.
RESULTS: Prenatal methamphetamine exposure was associated with significant DNA hypomethylation of four out of five CpG sites in the PCCB gene and three out of four CpG sites in the PCDHA12 gene. Also, significant hypomethylation in the biding site of p53 transcription factor in PCCB gene was detected in children with PME.
CONCLUSIONS: Prenatal methamphetamine exposure is related to epigenetic alterations in PCCB and PCDHA12, as important mitochondria function associated genes. Detected hypomethylation in these genes was reported in neurodevelopmental and bioenergetics disabilities. It seems that PME could cause mitochondrial dysfunctions associated with developmental abnormalities. What this paper adds?
OBJECTIVE: Clarification of PME role in methylation level of two mitochondria function associated genes; PCCB and PCDHA12.
METHODS: In this study, 2629 children with PME (1531male, 1098 female) and 3523(2077male, 1446 female) control children were recruited based on maternal self-report of prenatal exposure. Genomic DNA extracted from peripheral blood and pyrosequencing was used to determine the association between prenatal MA exposure and methylation in nine CpG sites of PCCB and PCDHA12 genes.
RESULTS: Prenatal methamphetamine exposure was associated with significant DNA hypomethylation of four out of five CpG sites in the PCCB gene and three out of four CpG sites in the PCDHA12 gene. Also, significant hypomethylation in the biding site of p53 transcription factor in PCCB gene was detected in children with PME.
CONCLUSIONS: Prenatal methamphetamine exposure is related to epigenetic alterations in PCCB and PCDHA12, as important mitochondria function associated genes. Detected hypomethylation in these genes was reported in neurodevelopmental and bioenergetics disabilities. It seems that PME could cause mitochondrial dysfunctions associated with developmental abnormalities. What this paper adds?
摘要：
背景：在怀孕期间使用甲基苯丙胺是重要的公共卫生问题，因为它会影响儿童的大脑发育和不良行为结果。产前暴露于甲基苯丙胺（PME）可能会导致发育障碍以及几种基因表达和分子途径的改变。在本研究中,在两组三岁儿童中评估了丙酰辅酶A羧化酶亚基β（PCCB）和原钙粘蛋白α12（PCDHA12）基因的DNA甲基化，那些暴露于PME和健康控制儿童的人。
目的：阐明PME在PCCB和PCDHA12两个线粒体功能相关基因甲基化水平中的作用。
方法：在本研究中，2629名PME儿童（1531名男性，1098女性）和3523（2077男性，1446名女性）对照儿童是根据产妇产前暴露的自我报告招募的。从外周血中提取的基因组DNA和焦磷酸测序用于确定产前MA暴露与PCCB和PCDHA12基因的9个CpG位点甲基化之间的关联。
结果：产前甲基苯丙胺暴露与PCCB基因中五个CpG位点中的四个和PCDHA12基因中四个CpG位点中的三个显著的DNA低甲基化相关。此外，在PME患儿中检测到PCCB基因p53转录因子结合位点的明显低甲基化。
结论：产前甲基苯丙胺暴露与PCCB和PCDHA12的表观遗传改变有关，PCCB和PCDHA12是重要的线粒体功能相关基因。在神经发育和生物能学残疾中报道了这些基因中检测到的低甲基化。似乎PME可能导致与发育异常相关的线粒体功能障碍。这篇论文补充了什么？
目的：阐明PME在PCCB和PCDHA12两个线粒体功能相关基因甲基化水平中的作用。
方法：在本研究中，2629名PME儿童（1531名男性，1098女性）和3523（2077男性，1446名女性）对照儿童是根据产妇产前暴露的自我报告招募的。从外周血中提取的基因组DNA和焦磷酸测序用于确定产前MA暴露与PCCB和PCDHA12基因的9个CpG位点甲基化之间的关联。
结果：产前甲基苯丙胺暴露与PCCB基因中五个CpG位点中的四个和PCDHA12基因中四个CpG位点中的三个显著的DNA低甲基化相关。此外，在PME患儿中检测到PCCB基因p53转录因子结合位点的明显低甲基化。
结论：产前甲基苯丙胺暴露与PCCB和PCDHA12的表观遗传改变有关，PCCB和PCDHA12是重要的线粒体功能相关基因。在神经发育和生物能学残疾中报道了这些基因中检测到的低甲基化。似乎PME可能导致与发育异常相关的线粒体功能障碍。这篇论文补充了什么？
