Monozygotic (MZ) twins do not show complete concordance for many complex diseases; for example, discordance rates for autoimmune diseases are 20%–80%. MZ discordance indicates a role for epigenetic or environmental factors in disease. We used MZ twins discordant for psoriasis to search for genome-wide differences in DNA methylation and gene expression in CD4+ and CD8+ cells using Illumina's HumanMethylation27 and HT-12 expression assays, respectively. Analysis of these data revealed no differentially methylated or expressed genes between co-twins when analyzed separately, although we observed a substantial amount of small differences. However, combined analysis of DNA methylation and gene expression identified genes where differences in DNA methylation between unaffected and affected twins were correlated with differences in gene expression. Several of the top-ranked genes according to significance of the correlation in CD4+ cells are known to be associated with psoriasis. Further, gene ontology (GO) analysis revealed enrichment of biological processes associated with the immune response and clustering of genes in a biological pathway comprising cytokines and chemokines. These data suggest that DNA methylation is involved in an epigenetic dysregulation of biological pathways involved in the pathogenesis of psoriasis. This is the first study based on data from MZ twins discordant for psoriasis to detect epigenetic alterations that potentially contribute to development of the disease.
Vyšlo v časopise: DNA Methylation and Gene Expression Changes in Monozygotic Twins Discordant for Psoriasis: Identification of Epigenetically Dysregulated Genes. PLoS Genet 8(1): e32767. doi:10.1371/journal.pgen.1002454 Kategorie: Research Article prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1002454
1. ChandranVRaychaudhuriSP 2010 Geoepidemiology and environmental factors of psoriasis and psoriatic arthritis. J Autoimmun 34 J314 J321
2. GrjibovskiAMOlsenAOMagnusPHarrisJR 2007 Psoriasis in Norwegian twins: contribution of genetic and environmental effects. J Eur Acad Dermatol Venereol 21 1337 1343
3. BowcockAMKruegerJG 2005 Getting under the skin: the immunogenetics of psoriasis. Nat Rev Immunol 5 699 711
4. HolloxEJHuffmeierUZeeuwenPLJMPallaRLascorzJ 2008 Psoriasis is associated with increased β-defensin genomic copy number. Nat Genet 40 23 25
5. ZhangXJHuangWYangSSunLDZhangFY 2009 Psoriasis genome-wide association study identifies susceptibility variants within LCE gene cluster at 1q21. Nat Genet 41 205 210
6. de CidRRiveira-MunozEZeeuwenPLJMRobargeJLiaoW 2009 Deletion of the late cornified envelope LCE3B and LCE3C genes as a susceptibility factor for psoriasis. Nat Genet 41 211 215
7. LiuYHelmsCLiaoWZabaLCDuanS 2008 A genome-wide association study of psoriasis and psoriatic arthritis identifies new disease loci. PLoS Genet 4 e1000041 doi:10.1371/journal.pgen.1000041
8. NairRPDuffinKCHelmsCDingJStuartPE 2009 Genome-wide scan reveals association of psoriasis with IL-23 and NF-κB pathways. Nat Genet 41 199 204
9. Genetic Analysis of Psoriasis Consortium & the Wellcome Trust Case Control Consortium 2 2010 A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1. Nat Genet 42 985 990
10. SunLDChengHWangZXZhangAPWangPG 2010 Association analyses identify six new psoriasis susceptibility loci in the Chinese population. Nat Genet 42 1005 1009
11. EllinghausEEllinghausDStuartPENairRPDebrusS 2010 Genome-wide association study identifies a psoriasis susceptibility locus at TRAF3IP2. Nat Genet 42 991 995
12. HuffmeierUUebeSEkiciABBowesJGiardinaE 2010 Common variants at TRAF3IP2 are associated with susceptibility to psoriatic arthritis and psoriasis. Nat Genet 42 996 999
13. StuartPENairRPEllinghausEDingJTejasviT 2010 Genome-wide association analysis identifies three psoriasis susceptibility loci. Nat Genet 42 1000 1004
14. BowcockAM 2005 THE GENETICS OF PSORIASIS AND AUTOIMMUNITY. Annu Rev Genomics Hum Genet 6 93 122
15. FengBJSunLDSoltani-ArabshahiRBowcockAMNairRP 2009 Multiple Loci within the major histocompatibility complex confer risk of psoriasis. PLoS Genet 5 e1000606 doi:10.1371/journal.pgen.1000606
16. BallestarE 2009 Epigenetics Lessons from Twins: Prospects for Autoimmune Disease. Clin Rev Allergy Immunol 39 30 41
17. JavierreBMFernandezAFRichterJAl-ShahrourFMartin-SuberoJI 2010 Changes in the pattern of DNA methylation associate with twin discordance in systemic lupus erythematosus. Genome Res 20 170 179
18. GaraudSLe DantecCJousse-JoulinSHanrotel-SaliouCSarauxA 2009 IL-6 Modulates CD5 Expression in B Cells from Patients with Lupus by Regulating DNA Methylation. J Immunol 182 5623 5632
19. LeiWLuoYLeiWLuoYYanK 2009 Abnormal DNA methylation in CD4+ T cells from patients with systemic lupus erythematosus, systemic sclerosis, and dermatomyositis. Scand J Rheumatol 38 369 374
20. StricklandFMRichardsonBC 2008 Epigenetics in human autoimmunity. Autoimmunity 41 278 286
21. KruegerJGBowcockA 2005 Psoriasis pathophysiology: current concepts of pathogenesis. Ann Rheum Dis 64 Suppl 2 ii30 ii36
22. CuddapahSBarskiAZhaoK 2010 Epigenomics of T cell activation, differentiation, and memory. Curr Opin Immunol 22 341 347
23. LowesMABowcockAMKruegerJG 2007 Pathogenesis and therapy of psoriasis. Nature 445 866 873
24. EckhardtFLewinJCorteseRRakyanVKAttwoodJ 2006 DNA methylation profiling of human chromosomes 6, 20 and 22. Nat Genet 38 1378 1385
25. RakyanVKDownTAThorneNPFlicekPKuleshaE 2008 An integrated resource for genome-wide identification and analysis of human tissue-specific differentially methylated regions (tDMRs). Genome Res 18 1518 1529
26. BibikovaMChudinEWuBZhouLGarciaEW 2006 Human embryonic stem cells have a unique epigenetic signature. Genome Res 16 1075 1083
27. ChangMLiYYanCCallis-DuffinKPMatsunamiN 2007 Variants in the 5q31 cytokine gene cluster are associated with psoriasis. Genes Immun 9 176 181
28. DixonRAFDiehlREOpasERandsEVickersPJ 1990 Requirement of a 5-lipoxygenase-activating protein for leukotriene synthesis. Nature 343 282 284
29. TaylorJMStreetTLHaoLCopleyRTaylorMS 2009 Dynamic and Physical Clustering of Gene Expression during Epidermal Barrier Formation in Differentiating Keratinocytes. PLoS ONE 4 e7651 doi:10.1371/journal.pone.0007651
30. HolickMFChimehFNRayS 2003 Topical PTH (1–34) is a novel, safe and effective treatment for psoriasis: a randomized self-controlled trial and an open trial. Br J Dermatol 149 370 376
31. DennisGShermanBHosackDYangJGaoW 2003 DAVID: Database for Annotation, Visualization, and Integrated Discovery. Genome Biol 4 P3
32. HuangDWShermanBTLempickiRA 2008 Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protocols 4 44 57
33. NickoloffBJXinHNestleFOQinJZ 2007 The cytokine and chemokine network in psoriasis. Clin Dermatol 25 568 573
34. GhoreschiKWeigertCRöckenM 2011 Immunopathogenesis and role of T cells in psoriasis. Clin Dermatol 25 574 580
35. WilsonNJBonifaceKChanJRMcKenzieBSBlumenscheinWM 2007 Development, cytokine profile and function of human interleukin 17-producing helper T cells. Nat Immunol 8 950 957
36. O'SheaJJPaulWE 2010 Mechanisms underlying lineage commitment and plasticity of helper CD4+ T cells. Science 327 1098 1102
37. HarrisJRMagnusPTambsK 2002 The Norwegian Institute of Public Health Twin Panel: a description of the sample and program of research. Twin Res 5 415 423
38. HarrisJRMagnusPTambsK 2006 The Norwegian Institute of Public Health twin program of research: an update. Twin Res Hum Genet 9 858 864
39. BergemAL 2002 Norwegian Twin Registers and Norwegian twin studies–an overview. Twin Res 5 407 414
40. DuPKibbeWALinSM 2008 lumi: a pipeline for processing Illumina microarray. Bioinformatics 24 1547 1548
41. BellJTPaiAAPickrellJKGaffneyDJPique-RegiR 2011 DNA methylation patterns associate with genetic and gene expression variation in HapMap cell lines. Genome Biol 12 R10
42. SmythGK 2004 Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat Appl Genet Mol Biol 3 Article3
43. BenjaminiYHochbergY 1995 Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing. J R Stat Soc Ser B Stat Methodol 57 289 300
Zvýšte si kvalifikáciu online z pohodlia domova
Nemáte účet? Registrujte sa
Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.
