Poster Presentation Epigenetics 2013

Differential methylation of whole blood genomic DNA of preterm versus term infants at birth and 18 years of age (#118)

Christiane Theda 1 2 3 , Mark Cruickshank 4 , Alicia Oshlack 2 3 , Penny Sheehan 1 2 , Peter Davis 1 2 3 , Lex Doyle 1 2 3 , Jeffrey Craig 2 3
  1. Royal Women's Hospital, Melbourne, VIC, Australia
  2. University of Melbourne, Melbourne, Victoria, Australia
  3. Murdoch Childrens Research Institute, Melbourne, VIC, Australia
  4. Telethon Institute for Child Health Research, Perth, Western Australia, Australia

Extremely preterm infants (born <28 weeks gestation) undergo multiple medical interventions and can suffer short and long term ill-health as a consequence of their preterm birth. Medical interventions are stressful and postnatal nutrition/growth are adversely affected. Environment, stress and nutrition can persistently alter gene expression – we are investigating an epigenetic mechanism that may regulate these changes: DNA methylation.

We examined genome-wide DNA methylation profiles after extracting DNA from dried blood spots of 12 extremely preterm infants and 12 term probands obtained at birth and 18 years. DNA methylation was quantified using the Illumina Infinium Human Methylation 450 BeadChip array covering 485,000 genome wide CpGs. Blood from preterm infants show methylation differences compared to term infants’ and prematurity may impart an epigenetic legacy detectable later in life (analysis of 347,789 probes after stringent quality control, exclusion of X/Y probes and known polymorphisms): 1,555 probes were differentially methylated comparing preterm and term samples at birth (DMPs; significant at p<0.05 after adjustment for multiple testing); at 18 years, there were no significant DMPs detected when correcting for multiple testing. Comparing all preterm with all term samples identified 109 combined DMPs at a genome-wide level of significance (adjusted p<0.05).

We now discuss specifics of birth-DMPs and preterm birth associated DMPs that persist to early adulthood: At birth, the “top 25” DMPs include probes associated with the following genes: HMHA1, LGALS9B, PRR5L, LGALS9C, CHD5, ITIH1, VWF, GABBR1, IL21R, CHD4, DNAJC17, LPPR2, ZC3H12D and SLC35F3. The “top 25” probes with the lowest nominal p-values at 18 years include probes associated with SSBP4, KNDC1, PXDN, RTBDN, MAP1D, MYL9, DNAJC1H, LIPE, LAYN, MFSD4, PCSK9, UPK1B, ADAMTS5, AGPAT9, IREB2, TFRC, TTC32, TOX2. Comparing all preterm with all term samples, 11 of the 109 DMPs had a mean difference of beta>0.05; these included PCSK9, TRIM71, SLC44A4, GPC6 and NFYA gene loci as well as two intergenic CpG sites flanking a binding site for the EGR1 transcription factor.