PDF(Pubmed)
Abstract：
UNASSIGNED: Acne is a chronic inflammatory skin disease that affects the pilosebaceous follicle and is influenced by heredity, hormones, inflammation, and the environment. At present, the recognized pathogenesis mainly includes four categories: excessive sebum secretion, excessive Cutibacterium acnes proliferation, excessive keratinization of sebaceous glands in hair follicles, and inflammatory mechanisms. Previous studies have found that DNA methylation is closely related to some chronic inflammatory skin diseases, and there is evidence that DNA methylation is controlled by genetic factors, making us want to know the relationship between DNA methylation, genetic variation and acne.
UNASSIGNED: In our previous study, we performed genome-wide DNA methylation analysis in peripheral blood samples from 44 patients with severe acne and 44 unaffected normal subjects, and identified 23 differentially methylated probes (DMPs). In this study, we identified single nucleotide polymorphisms (SNPs) associated with severe acne by genome-wide association analysis in these 88 samples. To test the association between SNPs and DMPs, we conducted DNA methylation quantitative trait loci (methQTL) analysis. Next, causal inference testing (CIT) was used to determine whether genetic variation influences DNA methylation, which impacts disease phenotypes.
UNASSIGNED: We found 38,269 SNPs associated with severe acne. By methQTL analysis, we obtained 24 SNP-CpG pairs that reached the threshold (FDR < 0.05), which included 7 unique CpGs and 22 unique methQTL SNPs. After CIT analysis, we found that 11 out of 24 pairs of SNP-CpG showed a weakened SNP effect after adjustment for methylation, indicating a methylation-mediated relationship between SNPs and severe acne. These 11 SNP-CpG pairs consist of four unique CpG sites and 11 SNPs, of which three CpG sites, cg03020863, cg20652636, and cg19964325, are located on the gene body of PDGFD, the intron of SH2D6, and the 5\'UTR of the IL1R1 gene, respectively.
UNASSIGNED: During this study, the DNA methylation of certain genes was found to be influenced by genetic factors and mediated the risk of severe acne in a young Chinese male population, providing a new perspective on the pathogenesis of severe acne.
UNASSIGNED: In our previous study, we performed genome-wide DNA methylation analysis in peripheral blood samples from 44 patients with severe acne and 44 unaffected normal subjects, and identified 23 differentially methylated probes (DMPs). In this study, we identified single nucleotide polymorphisms (SNPs) associated with severe acne by genome-wide association analysis in these 88 samples. To test the association between SNPs and DMPs, we conducted DNA methylation quantitative trait loci (methQTL) analysis. Next, causal inference testing (CIT) was used to determine whether genetic variation influences DNA methylation, which impacts disease phenotypes.
UNASSIGNED: We found 38,269 SNPs associated with severe acne. By methQTL analysis, we obtained 24 SNP-CpG pairs that reached the threshold (FDR < 0.05), which included 7 unique CpGs and 22 unique methQTL SNPs. After CIT analysis, we found that 11 out of 24 pairs of SNP-CpG showed a weakened SNP effect after adjustment for methylation, indicating a methylation-mediated relationship between SNPs and severe acne. These 11 SNP-CpG pairs consist of four unique CpG sites and 11 SNPs, of which three CpG sites, cg03020863, cg20652636, and cg19964325, are located on the gene body of PDGFD, the intron of SH2D6, and the 5\'UTR of the IL1R1 gene, respectively.
UNASSIGNED: During this study, the DNA methylation of certain genes was found to be influenced by genetic factors and mediated the risk of severe acne in a young Chinese male population, providing a new perspective on the pathogenesis of severe acne.
摘要：
■痤疮是一种慢性炎症性皮肤病，影响毛囊皮脂腺，受遗传影响，荷尔蒙，炎症,和环境。目前,公认的发病机制主要包括四类:皮脂分泌过多,痤疮皮肤杆菌过度增殖，毛囊皮脂腺过度角质化，和炎症机制。以往的研究发现,DNA甲基化与一些慢性炎症性皮肤病密切相关,有证据表明DNA甲基化受遗传因素控制，让我们想知道DNA甲基化之间的关系，遗传变异和痤疮。
■在我们之前的研究中，我们对44例重度痤疮患者和44例未受影响的正常受试者的外周血样本进行了全基因组DNA甲基化分析。并鉴定了23种差异甲基化探针（DMPs）。在这项研究中,通过全基因组关联分析,我们在这88份样本中鉴定出与重度痤疮相关的单核苷酸多态性(SNPs).为了测试SNP和DMP之间的关联，我们进行了DNA甲基化数量性状位点（methQTL）分析。接下来,因果推断测试(CIT)用于确定遗传变异是否影响DNA甲基化，影响疾病表型。
■我们发现了38,269个与严重痤疮相关的SNP。通过methQTL分析，我们获得了24个达到阈值的SNP-CpG对（FDR<0.05），其中包括7个独特的CpG和22个独特的methQTLSNP。CIT分析后，我们发现，在调整甲基化后，24对SNP-CpG中有11对显示出减弱的SNP效应，表明SNP和严重痤疮之间存在甲基化介导的关系。这11个SNP-CpG对由4个独特的CpG位点和11个SNP组成，其中三个CpG网站，cg03020863、cg20652636和cg19964325位于PDGFD的基因体上,SH2D6的内含子和IL1R1基因的5UTR，分别。
■在这项研究中，发现某些基因的DNA甲基化受遗传因素的影响，并介导了中国年轻男性人群中严重痤疮的风险，为严重痤疮的发病机制提供了新的视角。
■在我们之前的研究中，我们对44例重度痤疮患者和44例未受影响的正常受试者的外周血样本进行了全基因组DNA甲基化分析。并鉴定了23种差异甲基化探针（DMPs）。在这项研究中,通过全基因组关联分析,我们在这88份样本中鉴定出与重度痤疮相关的单核苷酸多态性(SNPs).为了测试SNP和DMP之间的关联，我们进行了DNA甲基化数量性状位点（methQTL）分析。接下来,因果推断测试(CIT)用于确定遗传变异是否影响DNA甲基化，影响疾病表型。
■我们发现了38,269个与严重痤疮相关的SNP。通过methQTL分析，我们获得了24个达到阈值的SNP-CpG对（FDR<0.05），其中包括7个独特的CpG和22个独特的methQTLSNP。CIT分析后，我们发现，在调整甲基化后，24对SNP-CpG中有11对显示出减弱的SNP效应，表明SNP和严重痤疮之间存在甲基化介导的关系。这11个SNP-CpG对由4个独特的CpG位点和11个SNP组成，其中三个CpG网站，cg03020863、cg20652636和cg19964325位于PDGFD的基因体上,SH2D6的内含子和IL1R1基因的5UTR，分别。
■在这项研究中，发现某些基因的DNA甲基化受遗传因素的影响，并介导了中国年轻男性人群中严重痤疮的风险，为严重痤疮的发病机制提供了新的视角。
