Abnormal DNA methylation in peripheral blood mononuclear cells from patients with vitiligo.
BACKGROUND
Vitiligo is a skin disorder characterized by the destruction of melanocytes by autoreactive lymphocytes. The genetic and environmental factors that trigger the autoimmune response are poorly understood. However, alterations to epigenetic DNA methylation patterns contribute to many other autoimmune diseases.


OBJECTIVE
To investigate genomic and gene-specific DNA methylation levels in peripheral blood mononuclear cells (PBMCs) of patients with vitiligo and to relate any changes to the expression of genes that regulate methylation, as well as the autoimmune-related gene IL10.


METHODS
We quantified global methylcytosine levels in PBMCs from 20 patients with vitiligo and 20 healthy controls. mRNA levels of DNA methyltransferases (DNMTs), methyl-DNA binding domain proteins (MBDs) and interleukin (IL)-10 were measured by real-time reverse transcriptase-polymerase chain reaction. Methylation of an IL10 regulatory element domain was determined by bisulphite genomic sequencing.


RESULTS
Genomic DNA methylation in PBMCs of patients with vitiligo was increased relative to healthy controls (P = 0·012). DNMT1, MBD1, MBD3, MBD4 and MeCP2 expression was significantly higher than in control PBMCs (P = 0·013, 0·001, 0·005, 0·001 and 0·001, respectively). MBD1 and MBD3 expression correlated positively with global DNA methylation in vitiligo PBMCs (MBD1: r = 0·519, P = 0·019; MBD3: r = 0·529, P = 0·016). IL10 expression was significantly decreased (P = 0·030), and an IL-10 enhancer region was hypermethylated in vitiligo PBMCs compared with controls (P = 0·014).


CONCLUSIONS
These data show that levels of DNA methylation are altered in PBMCs of patients with vitiligo, and this may contribute to disease activity by affecting the expression of autoimmunity-related genes.
Zhao
M
M
Department of Dermatology, Epigenetic Research Center, Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, Hunan 410011, China.
Gao
F
F
Wu
X
X
Tang
J
J
Lu
Q
Q
D000328:Adult; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000097:blood / Q000235:genetics; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000097:blood; D005260:Female; D015870:Gene Expression; D006801:Humans; D016753:Interleukin-10 / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014820:Vitiligo / Q000235:genetics*; D055815:Young Adult
D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D016753:Interleukin-10; D004248:DNA (Cytosine-5-)-Methyltransferases