DNA甲基化与银屑病相关基因的研究进展

DNA甲基化作为重要的表观遗传学现象之一,对基因的表达、细胞分化与增殖等发挥重要的调控功能.银屑病是一种由多基因多因素共同作用的具有遗传背景的复杂疾病,其组织病理特征为表皮过度增殖等表现.近年来关于DNA甲基化与银屑病相关基因p14、p16、p21、HLA-C、SHP-1基因的研究成为热点.概述DNA甲基化机制及主要的甲基化检测方法,并阐述银屑病相关基因的甲基化的研究现状.     

多基因遗传性皮肤病的遗传易感性研究进展

近年来 ,多基因遗传性皮肤病 ,包括银屑病、系统性红斑狼疮、特应性皮炎和白癜风等的遗传和基因研究已取得了很大进展 ,对这些常见的复杂疾病已经定位到了基因水平。尤其是对银屑病遗传易感性的研究更是取得了令人瞩目的成就。综述对这 4种多基因遗传性皮肤病的遗传易感性研究的最新进展     

多基因遗传性皮肤病的遗传易感性研究进展

近年来，多基因遗传性皮肤病，包括银屑病、系统性红斑狼疮、特应性皮炎和白癜风等的遗传和基因研究已取得了很大进展，对这些常见的复杂疾病已经定位到了基因水平。尤其是对银屑病遗传易感性的研究更是取得了令人瞩目的成就。综述对这4种多基因遗传性皮肤病的遗传易感性研究的最新进展。     

肿瘤病死因子α与β基因多态性与寻常性银屑病的相关性研究

银屑病(psoriasis vulgar,PV)是一种临床常见的以红斑鳞屑为表现的慢性炎症性皮肤疾病,可分为4种临床类型:寻常性、关节病性、红皮病性和脓疱性,其中寻常性银屑病占99％以上.目前普遍认为,银屑病是在环境因素刺激下由遗传背景控制的免疫失衡性疾病,遗传流行病学和遗传学研究均证实,银屑病是一种多因子遗传模式的复杂疾病,它涉及到多个基因间的相互作用及基因与环境的交互作用[1-2].迄今为止,国内外的研究小组应用连锁分析的方法,在全基因组范围内发现10个银屑病易感基因位点,即PSORS 1～10,已载人人类孟德尔遗传在线(OMIM)数据库,其中PSORS 1(6p)被认为是银屑病最重要的易感位点,有研究发现该区域的肿瘤坏死因子(TNF)基因和银屑病相关,极可能是银屑病的一个重要候选基因[3-4].本文采用PCR-限制性片段长度多态(RFLP)方法,对TNFα-238和-308基因座和TNFβ+252基因座多态性与河南豫北地区汉族群体银屑病的关系进行初步探讨.     

银屑病的流行病学

银屑病有遗传背景,但其遗传方式尚不清楚,有证据表明该病为多基因遗传。除遗传因素外,环境暴露因素可促进疾病的发生,其中包括感染、吸烟、应激、药物和外伤等。银屑病并发关节炎较多,如无有关药物治疗,避免了医源性损害,疾病本身并无增加发生肿瘤的危险,而且和心血管疾病也无实质上的联系。为确定银屑病发生和加重的危险因素,估计治疗的危险和效益,应进行认真对照的分析性和实验性流行病学研究。     

当今银屑病的防治策略

目前认为,银屑病是一多因素诱导、多基因遗传的慢性炎症性皮肤病,这些因素形成一个网络,导致了银屑病发病的多中心性和银屑病防治的复杂性。分子流行病学、分子遗传学的研究表明,银屑病符合多基因或多因子遗传特征。     

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.     

银屑病发病易感基因与表观遗传调控研究进展

银屑病是一种常见的慢性炎症性皮肤病，它是一种复杂的多因素性疾病，确切发病机制尚不明确，位于主要组织相容性复合体区域染色体6p21.3上的主要效应基因所起的遗传效应只占银屑病遗传可能性的三分之一，因此这不能完全解释银屑病的发病机制。研究发现，表观遗传学机制也参与银屑病的发病，如DNA甲基化、乙酰化修饰和MicroRNA调节。本文对银屑病发病易感基因及表观遗传调控进展进行综述。     

银屑病免疫学发病机制及相关转基因动物模型研究进展

银屑病是多基因遗传背景下的T细胞介导的免疫性疾病,其病因和发病机制复杂,且极少自然发生于人类以外的其它动物,所以,银屑病在免疫学方面的进展及相关动物模型的建立对于明确疾病的病因和机制以及治疗十分重要.     

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。     

GENETICS OF PSORIASIS AND PSORIATIC ARTHRITIS

It is well established that psoriasis and psoriatic arthritis (PsA) have a strong genetic component. Recent advances in genetics have confirmed previous associations and new loci have been discovered. However, these loci do not fully account for the high heritability of psoriasis and PsA and therefore many genetic as well as environmental factors remain to be identified. This paper reviews the current status of genetic studies in psoriasis and PsA.     

Genetic susceptibility to psoriasis and psoriatic arthritis: implications for therapy

The era of genome-wide association studies has revolutionized the search for genetic susceptibility loci in complex genetic conditions such as psoriasis. There are currently 16 loci with confirmed evidence for association with psoriasis susceptibility but there is the potential for more to be discovered as the genetic heritability of the disease has not yet been fully explained. Many of the associated loci overlap with those for psoriatic arthritis. In contrast to psoriasis susceptibility, few studies have been performed to identify predictors of drug response in psoriasis. As large-scale collaborations and registries for psoriasis and psoriatic arthritis are established, it is likely that a genome-wide approach may be used as a more effective method of searching for genetic predictors of treatment response. However, candidate gene studies will still have a role; for example, it is likely that some disease susceptibility genes will also be markers of treatment response, based on evidence from other diseases. This review summarizes recent advances in investigating the role genetics plays in psoriasis susceptibility and contrasts these to advances made in psoriatic arthritis. Further, it describes the genetics of treatment response in the two diseases and indicates how susceptibility loci could be used to identify drug response in the future.     

Unraveling oral psoriasis and its relationship with geographic tongue: A literature review

Differentiating between oral psoriasis and geographic tongue is difficult and controversial because some patients with geographic tongue do not necessarily have psoriasis. Furthermore, the number of clinical studies, reporting histopathological and genetic evidence for the definitive diagnosis of oral psoriasis, is limited. The aim of this literature review was to obtain data for supporting the diagnosis of oral psoriasis with particular emphasis on the relationship between psoriasis and geographic tongue. Based on the current data, it can be concluded that geographic tongue is the most common oral lesion in psoriasis, and histopathological, immunohistochemical, and genetic similarities have been observed between the two diseases. This review also emphasizes the importance of conducting oral examinations in patients with psoriasis and skin examinations in patients with geographic tongue.     

An association between psoriasis and hereditary multiple exostoses. A clue for the mapping of a psoriasis susceptibility gene?

Summary Chronic plaque psoriasis affects approximately 1·6% of the U.K. population. Population, family and twin studies all strongly suggest an important genetic component in the pathogenesis of the disease, although genetic linkage studies have, so far, failed to identify susceptibility genes. We describe a family in which psoriasis cosegregates through three generations with a known autosomal dominant disorder, hereditary multiple exostoses (HMK). A major locus for HMH has recently been mapped to chromosome 8q. Observations in this family may provide a mapping clue for a psoriasis susceptibility gene.     

A review of the epidemiology of psoriasis vulgaris in the community

Standard diagnostic criteria for epidemiological studies of psoriasis are currently lacking. In their absence, clinical examination and diagnosis of psoriasis by dermatologists provides the gold standard to underpin epidemiological research in psoriasis. The methods of data collection used most frequently include cross-sectional studies, case-control studies, cohort studies, and surveys of hospital and private practice attendance. Estimates of psoriasis prevalence made in cross-sectional studies employing clinical examinations as the survey instrument have ranged from 0.3 to 2.5%. Psoriasis incidence has been estimated at 60.4 per 100 000 person years in one cohort study. Several factors have been identified as being associated either with causation of psoriasis or with triggering exacerbations or remissions, including genetic determinants, racial and regional variation, injury and infection, cigarette smoking, alcohol, diet and other diseases.     

Recent developments in the understanding of the pathogenesis of psoriasis

Recent studies have provided new insights into the molecular mechanisms involved in the pathogenesis of psoriasis. Patients may inherit a predisposition to psoriasis, although the disease is expressed only after being triggered by certain environmental or antigenic factors. There is considerable genetic heterogeneity in psoriasis and several genetic loci associated with the occurrence of the disease have been identified. Although the underlying abnormality in psoriasis has not been definitively identified, recent evidence suggests that activated T lymphocytes play an important role in the pathogenesis of the disease. The activation of T lymphocytes can be mediated through antigen-presenting cells or through autoimmunity, and is influenced by cytokines. Recently developed animal models and in vitro studies of psoriasis have provided new evidence for the role of pathogenic lymphocytes in the initiation of the disease process. Further research will help to identify the susceptibility genes involved in psoriasis and provide a more complete understanding of the immunological basis of the disease. This should lead to the development of targeted therapies with improved efficacy and tolerability compared with some currently available treatments.     

Meta-analysis confirms the LCE3C_LCE3B deletion as a risk factor for psoriasis in several ethnic groups and finds interaction with HLA-Cw6

A multicenter meta-analysis including data from 9,389 psoriasis patients and 9,477 control subjects was performed to investigate the contribution of the deletion of genes LCE3C and LCE3B, involved in skin barrier defense, to psoriasis susceptibility in different populations. The study confirms that the deletion of LCE3C and LCE3B is a common genetic factor for susceptibility to psoriasis in the European populations (OR(Overall) = 1.21 (1.15-1.27)), and for the first time directly demonstrates the deletion's association with psoriasis in the Chinese (OR = 1.27 (1.16-1.34)) and Mongolian (OR = 2.08 (1.44-2.99)) populations. The analysis of the HLA-Cw6 locus showed significant differences in the epistatic interaction with the LCE3C and LCE3B deletion in at least some European populations, indicating epistatic effects between these two major genetic contributors to psoriasis. The study highlights the value of examining genetic risk factors in multiple populations to identify genetic interactions, and indicates the need of further studies to understand the interaction of the skin barrier and the immune system in susceptibility to psoriasis.     

链球菌感染在银屑病发病中的研究进展

链球菌感染与银屑病的相关性近年来得到人们的关注。银屑病发病的上呼吸道感染病史、咽拭子培养链球菌以及控制链球菌感染治疗银屑病的临床现象均提示银屑病发病与链球菌感染密切相关。银屑病是一类由T细胞介导的自身免疫性疾病，链球菌抗原可在易感人群中诱发或加重银屑病和使银屑病慢性持续存在，HLA的遗传多态性可能与此有关。本中将链球菌感染与银屑病发病相关性的临床研究，可能涉及的体液免疫、细胞免疫及遗传易感性方面的研究进展进行综述。     

瘦素及其受体与银屑病相关性的研究进展

银屑病是一种T细胞介导的以角质形成细胞过度增殖为特征的慢性炎症性皮肤病,其发病机制尚未阐明,可能是由遗传因素、免疫因素、环境因素、肥胖等多种因素互相作用的多基因遗传病。近来,临床研究发现,银屑病伴发肥胖的比例增高,针对肥胖治疗后有助于银屑病好转,提示肥胖与银屑病密切相关。瘦素是参与机体代谢的脂肪因子,以往研究表明,瘦素与其受体在银屑病皮损中高表达,瘦素可能与银屑病的表皮过度增生相关,提示瘦素与银屑病和肥胖可能存在内在分子联系。     

Psoriasis vulgaris and human leukocyte antigens

BACKGROUND: Psoriasis vulgaris is a skin disease with a complex immunological and genetic background, triggered by environmental factors. The association of human leukocyte antigens (HLA) and psoriasis has long been reported on population and familial studies. OBJECTIVES: To review and discuss studies on psoriasis vulgaris and HLA, in Caucasian and non-Caucasian populations. METHODS: The major population studies on psoriasis vulgaris and the associated HLA antigens and alleles are described and discussed based on a review of the current literature. RESULTS: Population studies demonstrate the presence of different HLA specificities as well as extended haplotypes in patients with psoriasis, when compared to controls. Some alleles occur in a lower frequency in patients with psoriasis, indicating they could be protection alleles. In all studies which HLA class I was typed, Cw6 or Cw*0602 was present in a significant frequency in patients with psoriasis, mainly when early onset and positive family history were considered. HLA-DRB1*0701 was also present in a higher frequency in patients in different populations. CONCLUSIONS: Different antigens and alleles from both HLA classes I and II were seen in a significantly higher frequency in patients with psoriasis vulgaris. HLA Cw*0602 and DRB1*0701 were represented in different reports, and the former was related mainly to psoriasis type I.