Psoriasis is a chronic inflammatory autoimmune skin disorder. Several studies suggested psoriasis to be a complex multifactorial disease, but the exact triggering factor is yet to be determined. Evidences suggest that in addition to genetic factors, epigenetic reprogramming is also involved in psoriasis development. Major histopathological features, like increased proliferation and abnormal differentiation of keratinocytes, and immune cell infiltrations are characteristic marks of psoriatic skin lesions. Following therapy, histopathological features as well as aberrant DNA methylation reversed to normal levels. To understand the role of DNA methylation in regulating these crucial histopathologic features, we investigated the genome-wide DNA methylation profile of psoriasis patients with different histopathological features. Genome-wide DNA methylation profiling of psoriatic and adjacent normal skin tissues identified several novel differentially methylated regions associated with psoriasis. Differentially methylated CpGs were significantly enriched in several psoriasis susceptibility (PSORS) regions and epigenetically regulated the expression of key pathogenic genes, even with low-CpG promoters. Top differentially methylated genes overlapped with PSORS regions including S100A9, SELENBP1, CARD14, KAZN and PTPN22 showed inverse correlation between methylation and gene expression. We identified differentially methylated genes associated with characteristic histopathological features in psoriasis. Psoriatic skin with Munro’s microabscess, a distinctive feature in psoriasis including parakeratosis and neutrophil accumulation at the stratum corneum, was enriched with differentially methylated genes involved in neutrophil chemotaxis. Rete peg elongation and focal hypergranulosis were also associated with epigenetically regulated genes, supporting the reversible nature of these characteristic features during remission and relapse of the lesions. Our study, for the first time, indicated the possible involvement of DNA methylation in regulating the cardinal pathophysiological features in psoriasis. Common genes involved in regulation of these pathologies may be used to develop drugs for better clinical management of psoriasis.

/pdf/epigenome-wide-dna-methylation-regulates-cardinal-128mjf7i8e.pdf

Epigenome-wide DNA methylation regulates cardinal pathological features of psoriasis

Influence of ERAP1 and ERAP2 gene polymorphisms on disease susceptibility in different populations.

The roles of ERAP1 and ERAP2 in autoimmunity and cancer immunity: New insights and perspective.

Autoimmune and autoinflammatory conditions represent a group of disorders characterized by self-directed tissue damage due to aberrant changes in innate and adaptive immune responses These disorders possess widely varying clinical phenotypes and etiology; however, they share a number of similarities in genetic associations and environmental influences Whilst the pathogenic mechanisms of disease remain poorly understood, genome wide association studies (GWAS) have implicated a number of genetic loci that are shared between several autoimmune and autoinflammatory conditions Association of particular HLA alleles with disease susceptibility represents one of the strongest genetic associations Furthermore, recent GWAS findings reveal strong associations with single nucleotide polymorphisms in the endoplasmic reticulum aminopeptidase 1 (ERAP1) gene and susceptibility to a number of these HLA-associated conditions ERAP1 plays a major role in regulating the repertoire of peptides presented on HLA class I alleles at the cell surface, with the presence of single nucleotide polymorphisms in ERAP1 having a significant impact on peptide processing function and the repertoire of peptides presented The impact of this dysfunctional peptide generation on CD8+ T-cell responses has been proposed as a mechanism of pathogenesis diseases where HLA and ERAP1 are associated More recently, studies have highlighted a role for ERAP1 in innate immune-mediated pathways involved in inflammatory responses Here, we discuss the role of polymorphic ERAP1 in various immune cell functions, and in the context of autoimmune and autoinflammatory disease pathogenesis

/pdf/the-role-of-polymorphic-erap1-in-autoinflammatory-disease-4iruu492wu.pdf

The role of polymorphic ERAP1 in autoinflammatory disease.

The association of ERAP1 and ERAP2 single nucleotide polymorphisms and their haplotypes with psoriasis vulgaris is dependent on the presence or absence of the HLA-C*06:02 allele and age at disease onset.

Associations of ERAP1 coding variants and domain specific interaction with HLA-C∗06 in the early onset psoriasis patients of India

Psoriasis is a chronic inflammatory skin disorder. Several studies suggested psoriasis to be a complex multifactorial genetic disease, but the exact triggering factor is yet to be determined. Many psoriasis susceptibility loci are located near genes that belong to immunologic pathways, indicating that defective immune system might play a major role in psoriasis pathogenesis. Human leukocyte antigen (HLA)-Cw6 allele within the major histocompatibility complex (MHC) Class I region was found to be the most significantly associated allele. Several other genetic loci have been reported, but the risk assessed by these factors is variable across populations. Epistatic interactions between HLA-Cw6 and other susceptibility loci have also been demonstrated in some populations. Furthermore, recent studies have suggested the association of several genetic markers with the drug response. Genetic studies are thus important not only to identify markers for disease predisposition and pathogenesis but also to predict drug response and develop personalised medications.



Key Concepts 

Psoriasis is a common chronic inflammatory disease characterised by hyper-proliferating keratinocytes, with varying prevalence among different populations worldwide.
Population-, family- and twin-based studies have indicated a genetic predisposition in psoriasis; however, they cannot fully explain the disease pathogenesis.
Many of the strongly associated loci with psoriasis are also associated with the immune system.
HLA-Cw6 allele is the most important risk allele within the MHC Class I region.
Several genetic susceptibility loci show differential associations between ethnic populations, suggesting potential genetic heterogeneity of psoriasis across diverse ancestries.
Population-specific genetic association studies are essential to elucidate the actual causal variants and develop more targeted therapeutics.
The impact of genetic polymorphisms on the response to drugs has been demonstrated in psoriasis.
Development of such targeted treatment based on patients' genetic background (pharmacogenetics) is a prospective area for disease management in psoriasis.




Keywords:

psoriasis vulgaris;
genetic markers;
single-nucleotide polymorphism;
genome-wide association studies;
major histocompatibility complex;
HLA-Cw6;
immunogenetics;
pharmacogenetics;
cyclosporine A;
ustekinumab

Genetics of Psoriasis

Background and objective Chronic kidney disease (CKD) comprises a spectrum of pathophysiologic processes with increased cardiovascular disease (CVD) risk mediated mostly by endothelial dysfunction other than traditional risk factors. The present study is carried out to see the cardiovascular risk in CKD patients with special reference to the determinants of endothelial dysfunction. Materials and methods We enrolled 60 CKD patients along with 120 healthy controls in the age group 18-50 years belonging to the same ethnicity and localities. Demographic and clinico-laboratory information including markers of endothelial dysfunction were recorded followed by univariate and multivariate analyses to assess the relationship between CKD and CVD risk. Results Cases comprised of 60 CKD patients (mean age = 38.47±8.56 years) including 35 (58%) females and 25 (42%) males. Etiology in 43% of cases was idiopathically followed by diabetes and hypertension (42%) and obstructive uropathy (13%). On comparing the means of inflammatory markers between cases and controls, calcium phosphate product, c-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and neutrophil: lymphocyte (N:L) ratio was found to be significantly higher (p < 0.05) in cases as compared to controls but carotid intima-media thickness (CIMT) and low-density cholesterol (LDL) did not show a significant difference (p < 0.05). Conclusion Our study showed uniformly higher levels of inflammatory markers in cases irrespective of age and gender except for LDL and CIMT which uniquely showed a positive correlation with age. CKD patients require appropriate treatment and preventive measures for CVD with a high index of suspicion as endothelial dysfunction cannot be adequately gauged by traditional risk scoring methods.

/pdf/inflammation-and-its-determinants-in-patients-with-chronic-3qd8n5bk.pdf

Inflammation and Its Determinants in Patients With Chronic Kidney Disease: A Study From North Eastern Region of India

Introduction-As on today’s era, the changing lifestyle and eating pattern like Visamasana, Adhyasana,Ajirnasana & consumption of Virudhaharacauses disturbance of the normal physiology which makes them prone to RaktaDushti Vikara, Mukhapakais one of them. It is a painful and often recurrent inflammatory process of the oral mucosa seen commonly in all classes of society.Aim and Objectives -To study the efficacy of Yastimadhu churnain Mukhapakaon the basis of the principle of treatment of Raktapradoshaja Vikara(Shaman concept ofRaktapittaharikriya).Materials and Methods-30 no. of patients were selected and administered Yastimadhu Churna 5gm with luke warm water after food twice daily for a period of 15 days. All patients were investigated for Hb gm %, BSL before and after treatment. The collected data was distributed according to different demography and Prakriti Pareeksha. The assessment of the subjective and objective parameters was evaluated by the statistical w-test and paired t-test.Observation and result: -It has been observed that, the trial drug is statistically significant at level of 5% (p<0.5) to reduce both parameters.Discussion and Conclusion:-Finally it can be said that the trial drug could be best means for management of RaktaPradoshaja Vikara (Mukhapaka). During the entire duration of therapy, any adverse effect of the drug was not found

/pdf/a-critical-study-on-raktapradoshaja-vikarawith-its-principle-14cu7c2v.pdf

A Critical Study on Raktapradoshaja Vikarawith its Principle of Treatment (Mukhapaka)with Yastimadhu Churna.

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Anamika Das

Author Tools

Chat about Author

Papers

Associations of ERAP1 coding variants and domain specific interaction with HLA-C∗06 in the early onset psoriasis patients of India

Genetics of Psoriasis

Inflammation and Its Determinants in Patients With Chronic Kidney Disease: A Study From North Eastern Region of India

A Critical Study on Raktapradoshaja Vikarawith its Principle of Treatment (Mukhapaka)with Yastimadhu Churna.