Epigenome-wide DNA Methylation Regulates Cardinal Pathological Features of Psoriasis

Overview

Journal Clin Epigenetics

Publisher Biomed Central

Specialty Genetics

Date 2018 Aug 11

PMID 30092825

Citations 50

Authors

Aditi Chandra

Swapan Senapati

Sudipta Roy

Gobinda Chatterjee

Raghunath Chatterjee

Affiliations

Soon will be listed here.

Abstract

Background: Psoriasis is a chronic inflammatory autoimmune skin disorder. Several studies suggested psoriasis to be a complex multifactorial disease, but the exact triggering factor is yet to be determined. Evidences suggest that in addition to genetic factors, epigenetic reprogramming is also involved in psoriasis development. Major histopathological features, like increased proliferation and abnormal differentiation of keratinocytes, and immune cell infiltrations are characteristic marks of psoriatic skin lesions. Following therapy, histopathological features as well as aberrant DNA methylation reversed to normal levels. To understand the role of DNA methylation in regulating these crucial histopathologic features, we investigated the genome-wide DNA methylation profile of psoriasis patients with different histopathological features.

Results: Genome-wide DNA methylation profiling of psoriatic and adjacent normal skin tissues identified several novel differentially methylated regions associated with psoriasis. Differentially methylated CpGs were significantly enriched in several psoriasis susceptibility (PSORS) regions and epigenetically regulated the expression of key pathogenic genes, even with low-CpG promoters. Top differentially methylated genes overlapped with PSORS regions including S100A9, SELENBP1, CARD14, KAZN and PTPN22 showed inverse correlation between methylation and gene expression. We identified differentially methylated genes associated with characteristic histopathological features in psoriasis. Psoriatic skin with Munro's microabscess, a distinctive feature in psoriasis including parakeratosis and neutrophil accumulation at the stratum corneum, was enriched with differentially methylated genes involved in neutrophil chemotaxis. Rete peg elongation and focal hypergranulosis were also associated with epigenetically regulated genes, supporting the reversible nature of these characteristic features during remission and relapse of the lesions.

Conclusion: Our study, for the first time, indicated the possible involvement of DNA methylation in regulating the cardinal pathophysiological features in psoriasis. Common genes involved in regulation of these pathologies may be used to develop drugs for better clinical management of psoriasis.

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References

Yooyongsatit S, Ruchusatsawat K, Noppakun N, Hirankarn N, Mutirangura A, Wongpiyabovorn J . Patterns and functional roles of LINE-1 and Alu methylation in the keratinocyte from patients with psoriasis vulgaris. J Hum Genet. 2015; 60(7):349-55. DOI: 10.1038/jhg.2015.33. View

Sandoval-Talamantes A, Brito-Luna M, Fafutis-Morris M, Villanueva-Quintero D, Graciano-Machuca O, Ramirez-Duenas M . The 3'UTR 1188A/C polymorphism of IL-12p40 is not associated with susceptibility for developing plaque psoriasis in Mestizo population from western Mexico. Immunol Lett. 2014; 163(2):221-6. DOI: 10.1016/j.imlet.2014.10.004. View

Chandra A, Lahiri A, Senapati S, Basu B, Ghosh S, Mukhopadhyay I . Increased Risk of Psoriasis due to combined effect of HLA-Cw6 and LCE3 risk alleles in Indian population. Sci Rep. 2016; 6:24059. PMC: 4822143. DOI: 10.1038/srep24059. View

Wang H, Iakova P, Wilde M, Welm A, Goode T, Roesler W . C/EBPalpha arrests cell proliferation through direct inhibition of Cdk2 and Cdk4. Mol Cell. 2001; 8(4):817-28. DOI: 10.1016/s1097-2765(01)00366-5. View

Li L, Dahiya R . MethPrimer: designing primers for methylation PCRs. Bioinformatics. 2002; 18(11):1427-31. DOI: 10.1093/bioinformatics/18.11.1427. View

Riveira-Munoz E, He S, Escaramis G, Stuart P, Huffmeier U, Lee C . Meta-analysis confirms the LCE3C_LCE3B deletion as a risk factor for psoriasis in several ethnic groups and finds interaction with HLA-Cw6. J Invest Dermatol. 2010; 131(5):1105-9. PMC: 3386316. DOI: 10.1038/jid.2010.350. View

Mehta S, Singal A, Singh N, Bhattacharya S . A study of clinicohistopathological correlation in patients of psoriasis and psoriasiform dermatitis. Indian J Dermatol Venereol Leprol. 2009; 75(1):100. DOI: 10.4103/0378-6323.45241. View

Zhou F, Wang W, Shen C, Li H, Zuo X, Zheng X . Epigenome-Wide Association Analysis Identified Nine Skin DNA Methylation Loci for Psoriasis. J Invest Dermatol. 2016; 136(4):779-787. DOI: 10.1016/j.jid.2015.12.029. View

Lowes M, Suarez-Farinas M, Krueger J . Immunology of psoriasis. Annu Rev Immunol. 2014; 32:227-55. PMC: 4229247. DOI: 10.1146/annurev-immunol-032713-120225. View

10.

Hou R, Yin G, An P, Wang C, Liu R, Yang Y . DNA methylation of dermal MSCs in psoriasis: identification of epigenetically dysregulated genes. J Dermatol Sci. 2013; 72(2):103-9. DOI: 10.1016/j.jdermsci.2013.07.002. View

11.

Litjens N, van der Plas M, Ravensbergen B, Numan-Ruberg S, van Assen Y, Thio H . Psoriasis is not associated with IL-12p70/IL-12p40 production and IL12B promoter polymorphism. J Invest Dermatol. 2004; 122(4):923-6. DOI: 10.1111/j.0022-202X.2004.22427.x. View

12.

Chandra A, Ray A, Senapati S, Chatterjee R . Genetic and epigenetic basis of psoriasis pathogenesis. Mol Immunol. 2015; 64(2):313-23. DOI: 10.1016/j.molimm.2014.12.014. View

13.

Ruchusatsawat K, Wongpiyabovorn J, Protjaroen P, Chaipipat M, Shuangshoti S, Thorner P . Parakeratosis in skin is associated with loss of inhibitor of differentiation 4 via promoter methylation. Hum Pathol. 2011; 42(12):1878-87. DOI: 10.1016/j.humpath.2011.02.005. View

14.

Gu X, Boldrup L, Coates P, Fahraeus R, Nylander E, Loizou C . Epigenetic regulation of OAS2 shows disease-specific DNA methylation profiles at individual CpG sites. Sci Rep. 2016; 6:32579. PMC: 5004144. DOI: 10.1038/srep32579. View

15.

Dogra S, Yadav S . Psoriasis in India: prevalence and pattern. Indian J Dermatol Venereol Leprol. 2010; 76(6):595-601. DOI: 10.4103/0378-6323.72443. View

16.

Zhang P, Zhao M, Liang G, Yin G, Huang D, Su F . Whole-genome DNA methylation in skin lesions from patients with psoriasis vulgaris. J Autoimmun. 2013; 41:17-24. DOI: 10.1016/j.jaut.2013.01.001. View

17.

Schon M, Behmenburg C, Denzer D, Schon M . Pathogenic function of IL-1 beta in psoriasiform skin lesions of flaky skin (fsn/fsn) mice. Clin Exp Immunol. 2001; 123(3):505-10. PMC: 1906010. DOI: 10.1046/j.1365-2249.2001.01421.x. View

18.

Lu L, Katsaros D, de la Longrais I, Sochirca O, Yu H . Hypermethylation of let-7a-3 in epithelial ovarian cancer is associated with low insulin-like growth factor-II expression and favorable prognosis. Cancer Res. 2007; 67(21):10117-22. DOI: 10.1158/0008-5472.CAN-07-2544. View

19.

Nair R, Callis Duffin K, Helms C, Ding J, Stuart P, Goldgar D . Genome-wide scan reveals association of psoriasis with IL-23 and NF-kappaB pathways. Nat Genet. 2009; 41(2):199-204. PMC: 2745122. DOI: 10.1038/ng.311. View

20.

Roberson E, Liu Y, Ryan C, Joyce C, Duan S, Cao L . A subset of methylated CpG sites differentiate psoriatic from normal skin. J Invest Dermatol. 2011; 132(3 Pt 1):583-92. PMC: 3568942. DOI: 10.1038/jid.2011.348. View