Short report of an Iranian Prenatal Methamphetamine Exposure effect cohort showed DNA methylation alteration of mitochondria function associated genes

Abstract

BackgroundUse 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. AimsClarification of PME role in methylation level of two mitochondria function associated genes; PCCB and PCDHA12. Methods and proceduresIn 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. Outcomes and resultsPrenatal 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 and implicationsPrenatal 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?•Prenatal methamphetamine exposure affects developmental issues in newborns, especially in bioenergetic pathways that in turn may cause neurodevelopmental and neurodegenerative problems.•This is the first cohort study on prenatal methamphetamine exposure's role in DNA Methylation of mitochondria functions associated with genes.