Integration of Genome-Wide DNA Methylation and Transcription Uncovered Aberrant Methylation-Regulated Genes and Pathways in the Peripheral Blood Mononuclear Cells of Systemic Sclerosis

Table 3

(a) 12 upregulated MeDEGs identified in SSc

	HUGO gene :	Function in SSc or related pathology and reference
C3AR1	Complement C3a Receptor 1: Receptor for the chemotactic and inflammatory peptide anaphylatoxin C3a. This receptor stimulates chemotaxis, granule enzyme release and superoxide anion production.	Inflammatory response. [23]
CSTA	cystatin A: cysteine proteinase inhibitor, encoding Cystatin A, underlies exfoliative ichthyosis	Protease inhibitor in cell-cell adhesion in the basal and lower suprabasal layers. [24]
CTSZ	Cathepsin Z, lysosomal cysteine proteinase and member of the peptidase C1 family: susceptibility locus suggests a role for MC3R and CTSZ in human tuberculosis	Angiogenesis [25, 26]
CTSG	Cathepsin G, granule serine protease	Development of anti-cathepsin G antibodies in sera, function unknown.
		Angiogenesis [27]
		destruction of the lung matrix and acute inflammation propagation [28].
ELANE	Elastase, Neutrophil Expressed: mutations implicated in severe Congenital and cyclic neutropenia	Destruction of extracellular matrix [29, 30]
LTBR	Lymphotoxin Beta Receptor, a member of the tumor necrosis factor receptor superfamily	development of natural killer cells
NFE2	Nuclear Factor, Erythroid 2: Component of the NF-E2 complex essential for regulating the beta-globin control region	Transcription factor
ODF3B	Outer Dense Fiber Of Sperm Tails 3B	Involved in the pathogenic CD4 T cell in MS
PLAUR	Plasminogen Activator, Urokinase Receptor	Coagulation/fibrolytic system [31, 32]; Angiogenesis [33, 34]
SAMDC4A	Sterile Alpha Motif Domain Containing 4A: posttranscriptional regulator	No report on SSc or related disease
SPI1	Spi-1 Proto-Oncogene: transcriptional regulator	Transcription factor
ZYX	Zyxin: actin regulator in vascular smooth muscle	Coagulation [35]
		integrity of vasculature [36]

(b) 8 downregulated MeDEGs identified in SSc

	HUGO gene : function^b	Function in SSc or related pathology and reference
CXCR6	C-X-C Motif Chemokine Receptor 6, receptor for the C-X-C chemokine CXCL16	Angiogenesis [37, 38]
F2R	Coagulation Factor II Thrombin Receptor	Coagulation/fibrolytic system, fibrosis [39–41]
FYN	Src Family Tyrosine Kinase	Fibrosis [40, 42]
PAG1	Phosphoprotein Membrane Anchor With Glycosphingolipid Microdomains 1	Proliferation of lymphocytes
PRF1	Perforin 1, pore forming protein 1, crucial effector of T and NK cell-mediated cytolysis, highly homologous to complement component C9	cytotoxic activity [43–45]; vascular damage [46]
PRKCH	Protein Kinase C Eta, calcium-insensitive, but activated by diacylglycerol (DAG) and phosphatidylserine	Associated in stroke, but no report in SSc or related diseases
RASSF5	Ras Association Domain Family Member 5, Potential tumor suppressor.	No report on SSc or related disease
RUNX3	Runt Related Transcription Factor 3	Transcription factor, induction and suppressive function of Foxp3+ inducible T reg [47]

http://www.genecards.org.
^aHuman Genome Organization nomenclature.
^bGene function from GeneCards website.