RationaleDNA methylation plays an important role in gene transcription. Alterations of methylation patterns can contribute to the development of disease. We profiled the genome-wide DNA methylation status of whole blood cells in patients with Atopic Dermatitis (AD) with a history of Eczema Herpeticum (ADEH+), AD without EH (ADEH-) and non-atopic, healthy controls (NA).MethodsGenomic DNA was isolated from whole blood from 100 ADEH+, ADEH-, and NA subjects each (total n=300) and applied to Illumina Infinium Human Methylation450 BeadChips.ResultsStatistically significant methylation differences were identified between the following groups: ADEH- versus NA (24), ADEH+ versus NA (2963), ADEH+ versus ADEH- (558). Inspection of the ADEH+ significant probe/genes revealed an unusual skew in the data in which 94% of the up- or down-regulated significant probes/ genes were incrementally increased or decreased from NA to ADEH+ patients. These patterns are following an additive model in which methylation is specifically increased in a stepwise fashion from healthy controls to ADEH+ patients with ADEH- patients as an intermediate stage. Preliminary results demonstrate a very high probability this model is accurate (hypergeometic test p<1E-14).ConclusionsPatterns of increasing methylation (ADEH+→ ADEH-→ NA) but not decreasing methylation (ADEH+← ADEH- ←NA) are specifically enriched for gene/probes involved in cellular differentiation (p<5.3E-08), chromosomal rearrangement (p<2.2E-05), and transcription (p<1.1E-04). In particular, included in this group are 28 homeodomain genes (e.g. HOXA5, HOXB2, HOXC4), gene/probes in control of the cell cycle (e.g. cyclins A1 and D2), as well as major transcription factors specifically involved in development (e.g. MYC, FOXO1, FOXP1, NFIA, NFIC). RationaleDNA methylation plays an important role in gene transcription. Alterations of methylation patterns can contribute to the development of disease. We profiled the genome-wide DNA methylation status of whole blood cells in patients with Atopic Dermatitis (AD) with a history of Eczema Herpeticum (ADEH+), AD without EH (ADEH-) and non-atopic, healthy controls (NA). DNA methylation plays an important role in gene transcription. Alterations of methylation patterns can contribute to the development of disease. We profiled the genome-wide DNA methylation status of whole blood cells in patients with Atopic Dermatitis (AD) with a history of Eczema Herpeticum (ADEH+), AD without EH (ADEH-) and non-atopic, healthy controls (NA). MethodsGenomic DNA was isolated from whole blood from 100 ADEH+, ADEH-, and NA subjects each (total n=300) and applied to Illumina Infinium Human Methylation450 BeadChips. Genomic DNA was isolated from whole blood from 100 ADEH+, ADEH-, and NA subjects each (total n=300) and applied to Illumina Infinium Human Methylation450 BeadChips. ResultsStatistically significant methylation differences were identified between the following groups: ADEH- versus NA (24), ADEH+ versus NA (2963), ADEH+ versus ADEH- (558). Inspection of the ADEH+ significant probe/genes revealed an unusual skew in the data in which 94% of the up- or down-regulated significant probes/ genes were incrementally increased or decreased from NA to ADEH+ patients. These patterns are following an additive model in which methylation is specifically increased in a stepwise fashion from healthy controls to ADEH+ patients with ADEH- patients as an intermediate stage. Preliminary results demonstrate a very high probability this model is accurate (hypergeometic test p<1E-14). Statistically significant methylation differences were identified between the following groups: ADEH- versus NA (24), ADEH+ versus NA (2963), ADEH+ versus ADEH- (558). Inspection of the ADEH+ significant probe/genes revealed an unusual skew in the data in which 94% of the up- or down-regulated significant probes/ genes were incrementally increased or decreased from NA to ADEH+ patients. These patterns are following an additive model in which methylation is specifically increased in a stepwise fashion from healthy controls to ADEH+ patients with ADEH- patients as an intermediate stage. Preliminary results demonstrate a very high probability this model is accurate (hypergeometic test p<1E-14). ConclusionsPatterns of increasing methylation (ADEH+→ ADEH-→ NA) but not decreasing methylation (ADEH+← ADEH- ←NA) are specifically enriched for gene/probes involved in cellular differentiation (p<5.3E-08), chromosomal rearrangement (p<2.2E-05), and transcription (p<1.1E-04). In particular, included in this group are 28 homeodomain genes (e.g. HOXA5, HOXB2, HOXC4), gene/probes in control of the cell cycle (e.g. cyclins A1 and D2), as well as major transcription factors specifically involved in development (e.g. MYC, FOXO1, FOXP1, NFIA, NFIC). Patterns of increasing methylation (ADEH+→ ADEH-→ NA) but not decreasing methylation (ADEH+← ADEH- ←NA) are specifically enriched for gene/probes involved in cellular differentiation (p<5.3E-08), chromosomal rearrangement (p<2.2E-05), and transcription (p<1.1E-04). In particular, included in this group are 28 homeodomain genes (e.g. HOXA5, HOXB2, HOXC4), gene/probes in control of the cell cycle (e.g. cyclins A1 and D2), as well as major transcription factors specifically involved in development (e.g. MYC, FOXO1, FOXP1, NFIA, NFIC).