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Reduced DNA methylation at the PEG3 DMR and KvDMR1 loci in children exposed to alcohol in utero : a South African Fetal Alcohol Syndrome cohort study
CITATION: Masemola, M. L. 2015. Reduced DNA methylation at the PEG3 DMR and KvDMR1 loci in children exposed to alcohol in utero : a South African Fetal Alcohol Syndrome cohort study. Frontiers in Genetics, 6:85, doi: 10.3389/fgene.2015.00085.The original publication is available at http://journal.frontiersin.org/journal/geneticsFetal alcohol syndrome (FAS) is a devastating developmental disorder resulting from
alcohol exposure during fetal development. It is a considerable public health problem
worldwide and is characterized by central nervous system abnormalities, dysmorphic facial
features, and growth retardation. Imprinted genes are known to play an important role in
growth and development and therefore four imprinting control regions (ICRs), H19 ICR,
IG-DMR, KvDMR1 and PEG3 DMR were examined. It is proposed that DNA methylation
changes may contribute to developmental abnormalities seen in FAS and which persist
into adulthood. The participants included FAS children and controls from the Western
and Northern Cape Provinces. DNA samples extracted from blood and buccal cells were
bisulfite modified, the ICRs were amplified by PCR and pyrosequencing was used to derive
a quantitative estimate of methylation at selected CpG dinucleotides: H19 ICR (six CpG
sites; 50 controls and 73 cases); KvDMR1 (7, 55, and 86); IG-DMR (10, 56, and 84); and
PEG3 DMR (7, 50, and 79). The most profound effects of alcohol exposure are on neuronal
development. In this study we report on epigenetic effects observed in blood which may
not directly reflect tissue-specific alterations in the developing brain. After adjusting for
age and sex (known confounders for DNA methylation), there was a significant difference
at KvDMR1 and PEG3 DMR, but not the H19 ICR, with only a small effect (0.84% lower
in cases; p D 0.035) at IG-DMR. The two maternally imprinted loci, KvDMR1 and PEG3
DMR, showed lower average locus-wide methylation in the FAS cases (1.49%; p < 0.001
and 7.09%; p < 0.001, respectively). The largest effect was at the PEG3 DMR though the
functional impact is uncertain. This study supports the role of epigenetic modulation as
a mechanism for the teratogenic effects of alcohol by altering the methylation profiles of
imprinted loci in a locus-specific manner.http://journal.frontiersin.org/article/10.3389/fgene.2015.00085/fullPublisher's versio