Abstract
BackgroundPsoriasis is a chronic inflammatory skin disease characterized by epidermal hyperproliferation and altered keratinocyte differentiation and inflammation and is caused by the interplay of genetic and environmental factors. Previous studies have revealed that DNA methylation (DNAm) and genetic makers are closely associated with psoriasis, and strong evidences have shown that DNAm can be controlled by genetic factors, which attracted us to evaluate the relationship among DNAm, genetic makers, and disease status.MethodsWe utilized the genome-wide methylation data of psoriatic skin (PP, N = 114) and unaffected control skin (NN, N = 62) tissue samples in our previous study, and we performed whole-genome genotyping with peripheral blood of the same samples to evaluate the underlying genetic effect on skin DNA methylation. Causal inference test (CIT) was used to assess whether DNAm regulate genetic variation and gain a better understanding of the epigenetic basis of psoriasis susceptibility.ResultsWe identified 129 SNP-CpG pairs achieving the significant association threshold, which constituted 28 unique methylation quantitative trait loci (MethQTL) and 34 unique CpGs. There are 18 SNPs were associated with psoriasis at a Bonferoni-corrected P < 0.05, and these 18 SNPs formed 93 SNP-CpG pairs with 17 unique CpG sites. We found that 11 of 93 SNP-CpG pairs, composed of 5 unique SNPs and 3 CpG sites, presented a methylation-mediated relationship between SNPs and psoriasis. The 3 CpG sites were located on the body of C1orf106, the TSS1500 promoter region of DMBX1 and the body of SIK3.ConclusionsThis study revealed that DNAm of some genes can be controlled by genetic factors and also mediate risk variation for psoriasis in Chinese Han population and provided novel molecular insights into the pathogenesis of psoriasis.Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-016-0297-z) contains supplementary material, which is available to authorized users.
Highlights
Psoriasis is a chronic inflammatory skin disease characterized by epidermal hyperproliferation and altered keratinocyte differentiation and inflammation and is caused by the interplay of genetic and environmental factors
Zhou et al Clinical Epigenetics (2016) 8:131 repressed when transfected into cultured mammalian cells, DNA methylation (DNAm) has been closely related with gene regulation
The methylation quantitative trait loci (MethQTL) CpG probes varied across annotated regions with 58.8% (20/34) locating on gene body and none locating on 3′ UTR or intergenic regions (Additional file 2: Figure S1)
Summary
Psoriasis is a chronic inflammatory skin disease characterized by epidermal hyperproliferation and altered keratinocyte differentiation and inflammation and is caused by the interplay of genetic and environmental factors. Previous studies have revealed that DNA methylation (DNAm) and genetic makers are closely associated with psoriasis, and strong evidences have shown that DNAm can be controlled by genetic factors, which attracted us to evaluate the relationship among DNAm, genetic makers, and disease status. Psoriasis is a chronic inflammatory skin disease with a complex etiology involving genetic risk factors and environmental triggers. Zhou et al Clinical Epigenetics (2016) 8:131 repressed when transfected into cultured mammalian cells, DNAm has been closely related with gene regulation. Epigenetics has been found to closely regulate gene expression; DNAm may affect the binding efficiency of transcription factors on gene regulatory elements. Several lines of evidences support the notion that sequence variations profoundly correlate with DNAm in human tissues and cultured cells [3], and this will pave the way for the development of new therapeutic strategies
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