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Correlation between Reversal of DNA Methylation and Clinical Symptoms in Psoriatic Epidermis Following Narrow-Band UVB Phototherapy.

Gu X, Nylander E, Coates PJ, Fahraeus R, Nylander K - J. Invest. Dermatol. (2015)

Bottom Line: Epigenetic modifications by DNA methylation are associated with a wide range of diseases.DNA methylation pattern was reversed at the end of phototherapy in patients showing excellent clinical improvement.Only 7% of phototherapy-affected MVPs (150 out of 2,108) correlate with nearby gene expression.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Biosciences/Pathology, Umeå University, Umeå, Sweden.

ABSTRACT
Epigenetic modifications by DNA methylation are associated with a wide range of diseases. Previous studies in psoriasis have concentrated on epigenetic changes in immune cells or in total skin biopsies that include stromal-associated changes. In order to improve our understanding of the role of DNA methylation in psoriasis, we sought to obtain a comprehensive DNA methylation signature specific for the epidermal component of psoriasis and to analyze methylation changes during therapy. Genome-wide DNA methylation profiling of epidermal cells from 12 patients undergoing narrow-band UVB phototherapy and 12 corresponding healthy controls revealed a distinct DNA methylation pattern in psoriasis compared with controls. A total of 3,665 methylation variable positions (MVPs) were identified with an overall hypomethylation in psoriasis patient samples. DNA methylation pattern was reversed at the end of phototherapy in patients showing excellent clinical improvement. Only 7% of phototherapy-affected MVPs (150 out of 2,108) correlate with nearby gene expression. Enrichment of MVPs in enhancers indicates tissue-specific modulation of the transcriptional regulatory machinery in psoriasis. Our study identified key epigenetic events associated with psoriasis pathogenesis and helps understand the dynamic DNA methylation landscape in the human genome.

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Related in: MedlinePlus

Score plot from PCA analysis for 12 psoriasis patients undergoing phototherapy and 12 corresponding controls. PCA score plot of the two first PCs of the methylation data set providing a map of how the samples relate to each other. The samples are colored by the sample group. Assessment of clinical response was given in three grades: Excellent, good, or unsatisfactory. POST-UV samples from patients with good or unsatisfactory response to phototherapy are indicated with symbol * or #, respectively.
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fig3: Score plot from PCA analysis for 12 psoriasis patients undergoing phototherapy and 12 corresponding controls. PCA score plot of the two first PCs of the methylation data set providing a map of how the samples relate to each other. The samples are colored by the sample group. Assessment of clinical response was given in three grades: Excellent, good, or unsatisfactory. POST-UV samples from patients with good or unsatisfactory response to phototherapy are indicated with symbol * or #, respectively.

Mentions: Principle component analysis (PCA) was performed to study sample similarities based on 2,108 MVPs. Figure 3 displays the score plot from principle component analysis showing first and second component that explains 75.1 and 4.8% of the variance, respectively. Samples close to each other have similar methylation profiles. We can see that control samples position closer to each other in the upper left-hand corner, whereas psoriasis samples before treatment are located most distal to the controls. It is also visualized that DNA methylation profiles in psoriasis changed following phototherapy to become more similar to the control group. Three POST-UV samples from patient 6, 7, and 9 are positioned in the upper right-hand corner, showing distinct methylation patterns compared with other POST-UV samples. Response assessment on the 11 patients that fulfilled treatment showed 7 patients with excellent clinical response, 2 with good response (patient 1, 9), and 2 with unsatisfactory response (patient 6, 7). When connecting clinical data to DNA methylation, we found that the DNA methylation status was associated with clinical outcome. All seven POST-UV samples from patients with excellent clinical improvement are positioned closer to the controls. The three particular POST-UV samples are from patients with unsatisfactory response (patient 6, 7) or good rather than excellent clinical improvement (patient 9). For the other POST-UV sample with good clinical improvement (patient 1), although appearing more similar to the controls following phototherapy, was positioned most distal to the controls in the lower left-hand corner.


Correlation between Reversal of DNA Methylation and Clinical Symptoms in Psoriatic Epidermis Following Narrow-Band UVB Phototherapy.

Gu X, Nylander E, Coates PJ, Fahraeus R, Nylander K - J. Invest. Dermatol. (2015)

Score plot from PCA analysis for 12 psoriasis patients undergoing phototherapy and 12 corresponding controls. PCA score plot of the two first PCs of the methylation data set providing a map of how the samples relate to each other. The samples are colored by the sample group. Assessment of clinical response was given in three grades: Excellent, good, or unsatisfactory. POST-UV samples from patients with good or unsatisfactory response to phototherapy are indicated with symbol * or #, respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4580729&req=5

fig3: Score plot from PCA analysis for 12 psoriasis patients undergoing phototherapy and 12 corresponding controls. PCA score plot of the two first PCs of the methylation data set providing a map of how the samples relate to each other. The samples are colored by the sample group. Assessment of clinical response was given in three grades: Excellent, good, or unsatisfactory. POST-UV samples from patients with good or unsatisfactory response to phototherapy are indicated with symbol * or #, respectively.
Mentions: Principle component analysis (PCA) was performed to study sample similarities based on 2,108 MVPs. Figure 3 displays the score plot from principle component analysis showing first and second component that explains 75.1 and 4.8% of the variance, respectively. Samples close to each other have similar methylation profiles. We can see that control samples position closer to each other in the upper left-hand corner, whereas psoriasis samples before treatment are located most distal to the controls. It is also visualized that DNA methylation profiles in psoriasis changed following phototherapy to become more similar to the control group. Three POST-UV samples from patient 6, 7, and 9 are positioned in the upper right-hand corner, showing distinct methylation patterns compared with other POST-UV samples. Response assessment on the 11 patients that fulfilled treatment showed 7 patients with excellent clinical response, 2 with good response (patient 1, 9), and 2 with unsatisfactory response (patient 6, 7). When connecting clinical data to DNA methylation, we found that the DNA methylation status was associated with clinical outcome. All seven POST-UV samples from patients with excellent clinical improvement are positioned closer to the controls. The three particular POST-UV samples are from patients with unsatisfactory response (patient 6, 7) or good rather than excellent clinical improvement (patient 9). For the other POST-UV sample with good clinical improvement (patient 1), although appearing more similar to the controls following phototherapy, was positioned most distal to the controls in the lower left-hand corner.

Bottom Line: Epigenetic modifications by DNA methylation are associated with a wide range of diseases.DNA methylation pattern was reversed at the end of phototherapy in patients showing excellent clinical improvement.Only 7% of phototherapy-affected MVPs (150 out of 2,108) correlate with nearby gene expression.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Biosciences/Pathology, Umeå University, Umeå, Sweden.

ABSTRACT
Epigenetic modifications by DNA methylation are associated with a wide range of diseases. Previous studies in psoriasis have concentrated on epigenetic changes in immune cells or in total skin biopsies that include stromal-associated changes. In order to improve our understanding of the role of DNA methylation in psoriasis, we sought to obtain a comprehensive DNA methylation signature specific for the epidermal component of psoriasis and to analyze methylation changes during therapy. Genome-wide DNA methylation profiling of epidermal cells from 12 patients undergoing narrow-band UVB phototherapy and 12 corresponding healthy controls revealed a distinct DNA methylation pattern in psoriasis compared with controls. A total of 3,665 methylation variable positions (MVPs) were identified with an overall hypomethylation in psoriasis patient samples. DNA methylation pattern was reversed at the end of phototherapy in patients showing excellent clinical improvement. Only 7% of phototherapy-affected MVPs (150 out of 2,108) correlate with nearby gene expression. Enrichment of MVPs in enhancers indicates tissue-specific modulation of the transcriptional regulatory machinery in psoriasis. Our study identified key epigenetic events associated with psoriasis pathogenesis and helps understand the dynamic DNA methylation landscape in the human genome.

Show MeSH
Related in: MedlinePlus