银屑病表观遗传学进展

银屑病是一种复杂的多基因遗传病,有家族遗传倾向,但并非每个子代均发病.表观遗传是指DNA序列不发生变化但基因表达却发生可遗传的改变,它从以下3个层面上调控基因的表达:DNA甲基化、组蛋白修饰及非编码RNA调控(如RNA干扰),与遗传印记、X染色体失活等临床现象有关.肿瘤及多种自身免疫性疾病都有表观遗传学的改变.综述银屑病表观遗传学方面的研究进展,以探讨银屑病的发病机制.     

银屑病的表观遗传研究进展

银屑病是一种反复发作的慢性炎症性疾病,发病机制非常复杂,其中遗传因素占有重要的地位.近年来有一系列研究表明,表观遗传机制参与银屑病的发病.表观遗传是指DNA序列不发生变化但基因表达却发生改变,且这种改变在发育和细胞增殖过程中能稳定传递,其主要机制为:DNA甲基化、组蛋白修饰及非编码RNA调控.银屑病表观遗传机制的研究对于寻找病因及探索更为有效的治疗方法意义重大,银屑病相关的表观遗传发现与研究,为该领域进一步的研究提供线索与方向.     

银屑病表观遗传修饰的研究

表观遗传学涉及机制主要包括DNA甲基化和组蛋白修饰及染色质重塑.这些因素共同构成基因的微环境来调控基因的转录.银屑病是一种病因不清的慢性炎症性皮肤病,目前有研究表明在银屑病的发生发展过程中,表观遗传修饰起着一定的修饰调节作用.银屑病的表观遗传学研究对银屑病的早期诊断和病情预后监测及其防治具有重要意义.     

表观遗传修饰异常与银屑病发病的相关性研究

目前认为，银屑病是遗传因素与环境因素等多种因素相互作用的多基因遗传病。表观遗传学是当前分子生物学领域研究的热点，本文就与银屑病相关基因的遗传修饰异常做一概述。     

银屑病的甲基化相关研究进展

银屑病是一种由多种因素相互作用而导致的多基因遗传病,表观遗传学是在基因表达水平发生的不涉及DNA序列改变的可遗传的变化,主要机制包括DNA甲基化、组蛋白修饰及非编码RNA调控。近年来许多证据表明银屑病的发病与表观遗传学有一定相关性,其中关于甲基化的研究较多,该文就银屑病的表观遗传学研究中甲基化方面进展进行综述。     

银屑病表观遗传调控的研究进展

【摘要】 研究显示，银屑病患者体内存在大量异常的表观遗传改变，包括DNA甲基化、组蛋白修饰、非编码RNA调节等，提示表观遗传机制可能参与了银屑病的发病。该文综述银屑病表观遗传调控的研究进展。     

银屑病表观遗传调控研究进展

银屑病是一种慢性炎症性增生性疾病,受到基因及环境等多种复杂因素的作用。其中包括表观遗传学,表观遗传可在不影响DNA序列改变的前提下,引起基因表达的稳定可遗传的改变,涉及DNA甲基化、非编码RNA调控、组蛋白修饰、基因印迹、x染色体失活等。银屑病患者具有明显的甲基化修饰异常,可致相应调控基因表达增多或减少;非编码RNA也可作用于相应靶点影响有关因子合成;组蛋白修饰异常参与银屑病角质形成细胞增殖异常。     

银屑病p53通路表观遗传机制的研究动态

p53途径是DNA损伤后介导细胞周期阻滞的关键路径,它的异常可导致细胞凋亡或过度增殖.众多表观遗传修饰模式如甲基化、乙酰化、磷酸化和泛素化等修饰导致的染色质重构是抑制p53表达的重要机制;银屑病是一类具有特征性细胞过度增殖的慢性炎症性皮肤病.p53途径中的p14ARF、MDM2、p21WAF1、Bcl-2/Bax、c-myc等效应分子以及缺氧诱导因子HIF-1α的表观遗传修饰机制参与了银屑病的发生.     

p15基因启动子区甲基化与新疆维吾尔族寻常性银屑病的相关性研究

正银屑病(psoriasis,PS)是一种常见并易复发的慢性炎症性皮肤病。根据PS临床特征,一般可分为4种类型:寻常性、脓疱性、关节病性及红皮病性银屑病。国内外研究表明,PS是多基因疾病,遗传和环境因素对其发病有至关重要的影响,但发病机制目前仍然不清楚。表观遗传学中DNA甲基化修饰影响和调控基     

脓疱型银屑病的病因及发病机制新进展

脓疱型银屑病是一种少见银屑病类型，是一种多基因控制下的免疫异常性皮肤病，其病因复杂。遗传因素、免疫机制、感染、药物等环境因素都参与发病。文中就脓疱型银屑病与感染、药物及HLA之间的关系进行综述。     

Epigenetics and psoriasis

Increasing evidence indicates that epigenetic mechanisms are involved in the pathogenesis of autoimmune rheumatic diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). The pathogenesis of the organ-specific autoimmune disease psoriasis, however, remains poorly understood. Recent studies have shown that aberrant epigenetic patterns are present in patients with psoriasis, suggesting that epigenetic mechanisms may also be involved in this disease. Herein, we review relevant epigenetic findings associated with psoriasis, and provide clues and directions for further studies in this field.     

Genetic aspects of psoriasis

Epidemiological studies indicate that genes play an important role in the pathogenesis of psoriasis. Multiple genes are likely to be involved, interacting not only with each other but also with the environment to cause disease expression. Molecular genetic studies indicate that there are multiple susceptibility loci present throughout the human genome. It is clear that a gene or genes of major impact on psoriasis is present on chromosome 6 within the major histocompatibility complex (MHC). Linkage disequilibrium studies indicate this gene to reside within a 300 kb interval centred around the centromeric end of class I MHC. Known candidate genes in this region are HLA-C, corneodesmosin and HCR, although novel genes, as yet unknown, may also exist. There is accumulating evidence that HLA-C is not itself the causative gene but rather a marker for it. Identification of the genes involved in psoriasis susceptibility will represent a step forward in our understanding of the disease and our future ability to help patients with psoriasis.     

微小RNA主导的免疫调节在银屑病发病机制中的研究现状

银屑病是一种慢性皮肤炎症性疾病,以炎症反应、角质形成细胞增殖加速和表皮更替频繁为主要病理特点,其发病机制复杂,由固有免疫、适应性免疫及其相关免疫细胞和细胞因子参与的免疫调节在其中发挥重要作用.微小RNA参与多种生物学过程,包括细胞增殖、分化、凋亡及器官形成和发育等,与机体免疫调节密切相关.微小RNA可能通过对T细胞、角质形成细胞、固有免疫细胞以及细胞因子的调控参与到银屑病发病.     

Genetic polymorphisms altering microRNA activity in psoriasis – a key to solve the puzzle of missing heritability?

Psoriasis is a chronic immune‐mediated skin disease in which the balance in the interplay of immune cells and keratinocytes is disturbed. MicroRNAs (miRNAs) are endogenous small regulatory RNAs that stabilize cellular phenotypes and fine‐tune signal transduction feedback loops through the regulation of gene networks. Through the regulation of their multiple target genes, miRNAs regulate the development of inflammatory cell subsets and have a significant impact on the magnitude of inflammatory responses. Since the discovery of deregulated miRNA expression in psoriasis, we have learned that they can regulate differentiation, proliferation and cytokine response of keratinocytes, activation and survival of T cells and the crosstalk between immunocytes and keratinocytes through the regulation of chemokine production. In recent years, it became apparent that genetic polymorphisms in miRNA genes and/or in miRNA binding sites of target genes can affect miRNA activity and contribute to disease susceptibility. Psoriasis has a strong genetic background; however, the contribution of genetic variants involving miRNAs is largely unexplored in psoriasis. We propose that changes in miRNA‐mediated gene regulation may be a major contributor to the disturbed balance in immune regulation that results in chronic skin inflammation. In this viewpoint essay, we focus on the emerging new aspects of the role of miRNAs in psoriasis and propose that genetic polymorphisms that affect miRNA activity might be important in the pathogenesis of psoriasis.     

A Study of Various Histopathological Features and their Relevance in Pathogenesis of Psoriasis

Background:

The pathogenesis of psoriasis is still to be fully unraveled. The immunological theory with T cells at the centre of attraction and peripherally acting cytokines are the present favourites among aetiopathological factors. Histopathology of the skin lesions offers a good study model to understand the pathogenesis of this complex disease.

Aims:

To study the various histopathological parameters of psoriatic lesions, and to establish their correlation with the pathogenesis of the disorder.

Materials and Methods:

Eighty eight consecutive histopathologically proven cases of psoriasis were included in the study. Eight common histopathological parameters of psoriasis present in these biopsies were assessed and graded. We then statistically analyzed the relationship of the factors with one another and attempted to establish a better understanding of the pathogenesis of disease.

Results:

Significant correlations were found between degree of epidermal hyperplasia and inflammatory infiltrate, grade of inflammation and pustules of Kogoj, inflammatory infiltrate and grade of capillary proliferation as also between epidermal hyperplasia and the presence of parakeratosis.

Conclusion:

The study suggests that the immunopathogenesis of psoriasis is predominantly based on the inflammatory response. This is in consonance with other studies which have suggested that psoriasis is primarily a T lymphocyte based disease. Several treatment modalities are now based on this concept and it is hoped that the future treatment modalities will focus on the central role of inflammatory cells in the pathogenesis of this enigmatic disease.     

Genetic analysis of PSORS1 distinguishes guttate psoriasis and palmoplantar pustulosis

The PSORS1 locus in the major histocompatibility complex region is the major genetic determinant for psoriasis vulgaris. Within the PSORS1 region reside at least three potential candidate genes for psoriasis susceptibility. Specific allelic variants of the genes HLA-Cw*6, HCR*WWCC, and CDSN*5 are strongly associated with psoriasis vulgaris and are in strong linkage disequilibrium with each other. We have genotyped the three psoriasis vulgaris susceptibility alleles of the PSORS1 locus in two clinical variants of psoriasis (guttate psoriasis and palmoplantar pustulosis) to study whether PSORS1 is also involved in the pathogenesis of these variants. We also asked whether these two clinical subgroups could help us to distinguish the causative gene within the high-risk PSORS1 haplotype. The association of guttate psoriasis with the three PSORS1 susceptibility alleles was similar and even stronger than seen with psoriasis vulgaris. Palmoplantar pustulosis, however, did not show association with any of the three candidate genes at this locus. Finally, no correlation with the age of onset for disease was observed. Our results show conclusively that psoriasis vulgaris and guttate psoriasis have a similar genetic basis for their association to PSORS1, whereas palmoplantar pustulosis appears to be a distinct disorder.     

miRNA调控银屑病角质形成细胞增殖机制的研究进展

MicroRNA（miRNA）在银屑病的发病过程中发挥重要作用,但其调节角质形成细胞增殖的机制尚未明了。本文对miRNA种类及在银屑病中的自调控方式进行了综述。     

Autosomal-dominant calcium ATPase disorders

Darier disease (DD) and Hailey-Hailey disease (HHD) are the only known autosomal-dominant Ca2+ ATPase disorders. Epidermal symptoms selectively occur in the affected individuals, the precise reason for which is still not fully understood. Here, we review the clinical, epidermal, and molecular features of the two genodermatoses. It is concluded that epidermal Ca2+ regulation disturbances and epigenetic factors may play an even more prominent role in the pathogenesis of DD and HHD than earlier appreciated.