title: Genome-Wide DNA Methylation Analysis of Chinese Patients with Systemic Lupus Erythematosus Identified Hypomethylation in Genes Related to the Type I Interferon Pathway.
abstract: BACKGROUND
  Epigenetic variants have been shown in recent studies to be important contributors to the pathogenesis of systemic lupus erythematosus (SLE). Here, we report a 2-step study of discovery followed by replication to identify DNA methylation alterations associated with SLE in a Chinese population. Using a genome-wide DNA methylation microarray, the Illumina Infinium HumanMethylation450 BeadChip, we compared the methylation levels of CpG sites in DNA extracted from white blood cells from 12 female Chinese SLE patients and 10 healthy female controls.
  
  
  RESULTS
  We identified 36 CpG sites with differential loss of DNA methylation and 8 CpG sites with differential gain of DNA methylation, representing 25 genes and 7 genes, respectively. Surprisingly, 42% of the hypomethylated CpG sites were located in CpG shores, which indicated the functional importance of the loss of DNA methylation. Microarray results were replicated in another cohort of 100 SLE patients and 100 healthy controls by performing bisulfite pyrosequencing of four hypomethylated genes, MX1, IFI44L, NLRC5 and PLSCR1. In addition, loss of DNA methylation in these genes was associated with an increase in mRNA expression. Gene ontology analysis revealed that the hypomethylated genes identified in the microarray study were overrepresented in the type I interferon pathway, which has long been implicated in the pathogenesis of SLE.
  
  
  CONCLUSIONS
  Our epigenetic findings further support the importance of the type I interferon pathway in SLE pathogenesis. Moreover, we showed that the DNA methylation signatures of SLE can be defined in unfractionated white blood cells.
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
authors.forename: Kit San
authors.initials: KS
authors.lastname: Yeung
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
authors.forename: Brian Hon-Yin
authors.initials: BH
authors.lastname: Chung
authors.affiliation: Genetics and Genome Biology Program, The Hospital for Sick Children Research Institute, Toronto, Canada.
authors.forename: Sanaa
authors.initials: S
authors.lastname: Choufani
authors.affiliation: Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.|Department of Biomedical Sciences, The City University of Hong Kong, Hong Kong, China.
authors.forename: Mo Yin
authors.initials: MY
authors.lastname: Mok
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
authors.forename: Wai Lap
authors.initials: WL
authors.lastname: Wong
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
authors.forename: Christopher Chun Yu
authors.initials: CC
authors.lastname: Mak
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
authors.forename: Wanling
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
authors.forename: Pamela Pui Wah
authors.initials: PP
authors.lastname: Lee
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
authors.forename: Wilfred Hing Sang
authors.initials: WH
authors.lastname: Wong
authors.affiliation: Genetics and Genome Biology Program, The Hospital for Sick Children Research Institute, Toronto, Canada.
authors.forename: Yi-An
authors.initials: YA
authors.lastname: Chen
authors.affiliation: Genetics and Genome Biology Program, The Hospital for Sick Children Research Institute, Toronto, Canada.
authors.forename: Daria
authors.initials: D
authors.lastname: Grafodatskaya
authors.affiliation: Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
authors.forename: Raymond Woon Sing
authors.initials: RW
authors.lastname: Wong
authors.affiliation: Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
authors.forename: Chak Sing
authors.initials: CS
authors.lastname: Lau
authors.affiliation: Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
authors.forename: Daniel Tak Mao
authors.initials: DT
authors.lastname: Chan
authors.affiliation: Genetics and Genome Biology Program, The Hospital for Sick Children Research Institute, Toronto, Canada.|Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, Ontario, Canada.|Institute of Medical Science and Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Weksberg
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
authors.forename: Yu-Lung
authors.initials: YL
authors.lastname: Lau
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism*; D016022:Case-Control Studies; D002681:China; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D053263:Gene Regulatory Networks; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D007370:Interferon Type I / Q000235:genetics*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D055815:Young Adult
chemical_list: D015415:Biomarkers; D007370:Interferon Type I