甲氨蝶呤治疗前后银屑病患者的全血 DNA 甲基化[5-甲基胞嘧啶 (5-mC)]水平

IF 1 Q4 GENETICS & HEREDITY Gene Reports Pub Date : 2024-11-07 DOI:10.1016/j.genrep.2024.102083
Veera Krishna Goud , Alladi Charanraj Goud , Sivaranjini Ramassamy , M. Jayanthi , R. Medha , Laxmisha Chandrashekar
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引用次数: 0

摘要

背景银屑病是一种慢性炎症性皮肤病,以角质细胞过度增殖和异常免疫反应为特征。它主要发生在易受感染、药物、压力和创伤等环境诱因影响的遗传易感人群中。表观遗传机制是银屑病复杂发病机制的重要组成部分,因为它们会调节基因表达并增加患病风险。关于银屑病患者的 DNA 甲基化,有许多相互矛盾的报道。这很可能反映了所选择的组织和所使用的技术。本研究旨在测量甲氨蝶呤治疗前后银屑病患者全血中 DNA 甲基化[5-甲基胞嘧啶(5-mC)]的水平及其与疾病严重程度的相关性。30 名银屑病患者接受了甲氨蝶呤治疗,并随访了三个月。结果病例全血DNA中的5-甲基胞嘧啶含量为8.13±1.89%,对照组为5.37±2.33%,差异有统计学意义(P = 0.0001)。甲氨蝶呤治疗后,病例的 5-甲基胞嘧啶水平(4.54±1.74 %)明显下降(p = 0.0001)。治疗前和治疗后的 5-甲基胞嘧啶水平与银屑病面积严重程度指数(PASI)评分无明显关联。结论银屑病患者的全血DNA整体高甲基化,甲氨蝶呤治疗可显著降低DNA高甲基化。
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Whole blood global DNA methylation [5-methylcytosine (5-mC)] levels in psoriatic patients before and after methotrexate treatment

Background

Psoriasis is a chronic inflammatory skin disease characterised by hyperproliferation of keratinocytes and abnormal immune response. It manifests in genetically predisposed individuals exposed to environmental triggers like infections, drugs, stress, and trauma. Epigenetic mechanisms are a critical component of the complex etiopathogenesis of psoriasis, as they modulate gene expression and increase disease risk. There are many conflicting reports regarding DNA methylation in patients with psoriasis. This could well reflect the choice of tissue and technique used. Data on whole blood DNA methylation in psoriasis is sparse.

Objective

The present study aims to measure the levels of DNA methylation [5-methylcytosine (5-mC)] in psoriatic patients from whole blood pre and post-treatment with methotrexate and its correlation with disease severity.

Methods

We recruited thirty cases of psoriasis vulgaris and 30 healthy controls. Thirty psoriatic patients were on methotrexate treatment and followed up for three months. 5-methylcytosine was measured using a global DNA methylation ELISA kit.

Results

The 5-methylcytosine levels from whole blood DNA were 8.13±1.89 % in cases and 5.37±2.33 % in controls, which was statistically significant (p = 0.0001). Post-treatment with methotrexate, there was a significant reduction (p = 0.0001) in the 5-methylcytosine levels in cases (4.54±1.74 %). Pre and post-treatment 5-methylcytosine levels were not significantly associated with the Psoriasis Area Severity Index (PASI) score.

Conclusion

Patients with psoriasis have whole-blood DNA global hypermethylation. Treatment with methotrexate leads to a significant reduction in DNA hypermethylation.
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来源期刊
Gene Reports
Gene Reports Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
3.30
自引率
7.70%
发文量
246
审稿时长
49 days
期刊介绍: Gene Reports publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses. Gene Reports strives to be a very diverse journal and topics in all fields will be considered for publication. Although not limited to the following, some general topics include: DNA Organization, Replication & Evolution -Focus on genomic DNA (chromosomal organization, comparative genomics, DNA replication, DNA repair, mobile DNA, mitochondrial DNA, chloroplast DNA). Expression & Function - Focus on functional RNAs (microRNAs, tRNAs, rRNAs, mRNA splicing, alternative polyadenylation) Regulation - Focus on processes that mediate gene-read out (epigenetics, chromatin, histone code, transcription, translation, protein degradation). Cell Signaling - Focus on mechanisms that control information flow into the nucleus to control gene expression (kinase and phosphatase pathways controlled by extra-cellular ligands, Wnt, Notch, TGFbeta/BMPs, FGFs, IGFs etc.) Profiling of gene expression and genetic variation - Focus on high throughput approaches (e.g., DeepSeq, ChIP-Seq, Affymetrix microarrays, proteomics) that define gene regulatory circuitry, molecular pathways and protein/protein networks. Genetics - Focus on development in model organisms (e.g., mouse, frog, fruit fly, worm), human genetic variation, population genetics, as well as agricultural and veterinary genetics. Molecular Pathology & Regenerative Medicine - Focus on the deregulation of molecular processes in human diseases and mechanisms supporting regeneration of tissues through pluripotent or multipotent stem cells.
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