红斑、丘疹及鳞屑性皮肤病

20110899银屑病相关的单核苷酸多态性(综述)/孙莉(胜利油田中心医院皮科),颜敏∥中国皮肤性病学杂志.-2010,24(12).-1154~1156单核苷酸多态性是第三代遗传标记物,是单个核苷酸变异引起的DNA多态性,是人类基因组中最常见、分布最广泛的DNA多态性。在对银屑病这种复杂性疾病的发病机制研究中,单核苷酸多态性提供了发现易感基因的新手段和新视角。现在认为有多种     

银屑病分子遗传学研究进展

银屑病是一种由环境因素和遗传因素共同作用的多因素的复杂疾病.既往研究多采取家系连锁分析、候选基因的方法,但其检测效能较低.目前基于第三代遗传标记的单核苷酸多态性寻找疾病易感基因的全基因组关联分析在复杂疾病的广泛应用,使得银屑病的遗传学发病基础研究进入新阶段,并可能为银屑病提供新的治疗靶点.     

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.     

早发型与晚发型银屑病的临床特点及遗传学研究

寻常性银屑病可根据年龄分为早发型与晚发型,许多学者就其遗传学和临床特点两方面进行了大量研究.最近的研究发现,早发型银屑病发病与等位基因rs10852936(17q12/IKZF3)突变等有关,晚发型银屑病发病则与白细胞介素1受体1等位基因中单核苷酸多态性rs887998、人白细胞抗原A中单核苷酸多态性rs2256919及等位基因人白细胞抗原C*12:02等有关.同时,地域间早发型与晚发型银屑病的临床特点也存在差异.早发型银屑病更易复发,易合并心理障碍;青春期发病患者发生点滴状皮损的概率高,且多与链球菌感染有关.晚发型银屑病易发生掌跖脓疱病、红皮病性银屑病,易合并糖耐量异常及肥胖症;老年发病患者家族史阳性率低,皮损较轻.     

寻常性银屑病患者白介素20基因多态性研究

目的:选取位于1q32区域的白介素(IL)-20基因,通过检测基因序列研究基因多态性与银屑病的相关性.方法:提取银屑病患者(203例)和正常人(91名)基因组DNA并进行扩增,通过自动测序的方法测定IL-20基因及启动子区域的序列,检测其单核苷酸多态性(SNP)位点,并以SPSS软件进行统计学处理.结果:①IL-20启动子SNP位点-1723 C>G多态性的G等位基因频率,在以上呼吸道感染为发病诱因或加重因素的寻常性银屑病患者组和正常对照组间的频率分别为45.8%和32.4%,两组间差异有统计学意义(X2=5.539,P=0.019).结论:位于IL-20基因启动子区的SNP位点-1723C>G可能与以上呼吸道感染为发病诱因或加重因素的寻常性银屑病相关.     

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。     

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。     

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。     

寻常型银屑病患者HLA-DQB1等位基因多态性分析

寻常型银屑病病因和发病机理迄今尚不清楚。遗传因素在寻常型银屑病的发病过程中具有重要作用。有关寻常型银屑病与ＨＬＡ相关性研究 ,１９８１年宋芳吉等曾有报道 ,以后又逐步发现中国人寻常型银屑病与Ａ１、Ｂ１３、Ｂ１７、Ｃｗ６和ＤＲ７相关。我们通过检测寻常型银屑病患者ＨＬＡ ＤＱＢ１等位基因的多态性分布情况 ,分析寻常型银屑病与ＤＱＢ１等位基因的关联 ,其结果可为探讨遗传因素在寻常型银屑病发病机制中的作用及为寻常型银屑病疾病易感基因的定位提供进一步线索。一、病例和方法（一）病例 :病例组 :中国汉族寻常型银屑病患者…     

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。     

Genetic polymorphisms of the HCR gene and a genomic segment in close proximity to HLA-C are associated with patients with psoriasis in Taiwan

BACKGROUND: Although psoriasis vulgaris (PV) is strongly associated with HLA-Cw*0602, it has been proposed that the association of Cw*0602 is due to linkage disequilibrium and that other nearby genes are involved in PV susceptibility. The alpha-helix coiled-coil rod homologue (HCR) gene, located 110 kb telomeric to the HLA-C locus, is presumed to be one of the PV candidate genes. Recently, a 10-kb genomic segment, centromeric to HLA-C, defined by two new single nucleotide polymorphisms (SNPs) n.7*A and n.9*C, was found to have a stronger association with psoriasis than the HCR gene. Until now, no study of the association of the HCR gene, SNPs n.7, and n.9 has been conducted on Chinese patients with psoriasis. OBJECTIVES: We aimed to determine whether the genetic polymorphisms of the HCR gene, SNPs n.7*A, and n.9*C were associated with an increased risk of psoriasis in Chinese patients. METHODS: Using direct sequencing of the HCR gene and the genomic region containing SNPs n.7 and n.9, we investigated the HCR gene, SNPs n.7, and n.9 for disease association in 115 Chinese patients with psoriasis and 103 control subjects. The HCR SNPs were confirmed by denaturing high performance liquid chromatography. Genotyping for HLA-Cw*0602 was also carried out using sequence-based typing. RESULTS: We observed a different allelic distribution between patient and control groups at nucleotide positions 386, 404, 1802 and 2406 of the HCR gene, and SNPs n.7, and n.9. The associations were much stronger in early onset PV patients (for HCR-386*T and HCR-404*T, odds ratio = 5.63, Pc < 0.0001). The HLA-Cw*0602 also displayed a similar association with PV (odds ratio = 5.4, Pc < 0.0001). Moreover, SNP n.7*A, SNP n.9*C, Cw*0602, HCR-386*T, HCR-404*T and HCR-1802*T were in linkage disequilibrium with each other. Haplotype-based association analysis showed SNP n.7*A-SNP n.9*C-Cw*0602-HCR-386*T-HCR-404*T-HCR-1802*T-HCR-2406*G as a major susceptibility haplotype in this Chinese population (for early onset patients, odds ratio = 5.15, Pc < 0.0001). CONCLUSIONS: Our results indicate that the HCR gene, SNP n.7*A, and SNP n.9*C as well as Cw*0602 are major susceptibility markers for psoriasis in Chinese patients.     

寻常性银屑病患者HAX-1基因多态性的研究

目的通过检测HAX-1基因序列研究基因多态性与银屑病的相关性。方法提取银屑病患者(247例)和正常人(102例)基因组DNA并进行扩增,通过自动测序的方法测定HAX-1基因及启动子区域的序列,检测其SNP位点,并以SPSS软件进行统计处理。结果①测序结果:测序总长度5313bp,发现1个位于5’UTR的高频SNP。②病例-对照关联分析结果:5’UTR区的SNP位点-104T>G多态性的T等位基因频率在寻常性银屑病患者组和正常对照组间的频率分别为53.4%和48.5%,在两组间无显著性差异(P>0.05)。结论银屑病患者与正常人HAX-1基因5’UTR区的SNP位点-104T>G基因频率无显著差异。     

CARD15/NOD2 single nucleotide polymorphisms do not confer susceptibility to type I psoriasis

BACKGROUND: A psoriasis susceptibility locus on chromosome 16q was identified recently. This region coincides with a locus predisposing to Crohn's disease. Patients with Crohn's disease have a fivefold greater relative risk for development of psoriasis. In Crohn's disease mutation of the caspase recruitment domain family, member 15 (CARD15) gene (chromosome 16q12.1) confers susceptibility. In light of the overlap in linkage data, and the observation of comorbidity between Crohn's disease and psoriasis, it is plausible that both diseases share a common genetic factor. OBJECTIVES: To assess the genetic contribution of CARD15 single nucleotide polymorphisms (SNPs) in the pathogenesis of type I psoriasis. METHODS: Eight SNPs in CARD15 were genotyped in 148 patients with type I psoriasis and 192 unrelated controls, following a test for population stratification. Genotype and allele frequencies were compared along with estimated SNP haplotype frequencies. RESULTS: No differences were observed in genotype allele or haplotype frequencies between the case and control cohorts. CONCLUSIONS: The most complete assessment of CARD15 SNPs in type I psoriasis to date reveals no evidence of association to type I psoriasis.     

Analysis of manganese superoxide dismutase (MnSOD Ala-9Val) and glutathione peroxidase (GPx1 Pro 198 Leu) gene polymorphisms in psoriasis

Recent studies have suggested the involvement of increased reactive oxygen species levels and decreased antioxidant system functions in psoriasis pathogenesis. In this study, we aimed to examine to investigate possible associations between the manganese superoxide dismutase (MnSOD Ala-9Val) and glutathione peroxidase (GPx1 Pro198Leu) polymorphisms and psoriasis susceptibility and disease progression in a Turkish population. The study group consisted of 100 unrelated patients with psoriasis and 167 unrelated healthy controls. Genomic DNA was extracted from peripheral leukocytes of whole blood which were obtained from all patients and control subjects. Genotyping was performed to identify MnSOD Ala-9Val and GPx1 Pro198Leu polymorphisms by a method based on PCR amplification and detection of polymorphisms with hybridization probes labeled with fluorescent dyes. Genotype and allele frequencies were compared between patients with psoriasis and 106 healthy control subjects. There was no significant difference between the MnSOD Ala-9Val single nucleotide polymorphism (SNP) genotype distributions and allele frequencies of the psoriasis patients and the control group (p = 0.99 and p = 0.89, respectively). There was also no significant difference between distributions of the genotype or allele frequencies of the GPx1 Pro198Leu SNP of the patient groups and control subjects (p = 0.99 and p = 0.96, respectively). Also, no significant difference was found between clinical severity of psoriasis and MnSOD Ala-9Val and GPx1 Pro198Leu polymorphism. This is the first report investigating the possible associations between the MnSOD Ala-9Val and GPx1 Pro198Leu polymorphisms and psoriasis susceptibility and disease progression in the Turkish population even if no significant difference was found between patient groups and control subjects. Further studies with large cohort on different populations and ethnicities will be able to better clarify the association.     

IL-12B和IL-23R基因多态性与中国汉族人银屑病易感性关联研究

目的 探讨中国汉族人群中IL-12B和IL-23R基因多态性与银屑病易感性的关系。方法 在217例银屑病患者和288例正常人对照中,采用DNA直接测序法对IL-12B和IL-23R基因的多态性位点进行基因分型,并将阳性结果在一个更大的包括578例银屑病患者和1422例正常人对照的整合样本群中,使用Taqman探针荧光PCR技术进行重复检验。实验数据进行Hardy-Weinberg平衡检验、卡方检验、单倍型分析和Logistic回归模型分析。结果 IL-12B rs6887695位点等位基因频率在病例组与对照组之间差异有统计学意义,OR = 1.33（95% CI 1.03 ~ 1.73）,P = 0.028;IL-23R rs11465817和rs1343152位点等位基因频率在病例组与对照组之间差异无统计学意义（P > 0.05）。连锁不平衡分析发现,rs11465817和rs1343152位点之间有一定的连锁不平衡（D′ = 0.744,r2 = 0.281）。对2个位点进行单倍型分析发现,A-A ∶ OR = 2.890,P = 0.0018,提示这一单倍型具有显著的发病风险。结论 IL-12B基因rs6887695多态性与中国汉族人群银屑病易感性相关;IL-23R基因rs11465817、IL-23R基因rs1343152位点多态性与中国汉族人群银屑病易感性无显著相关性,但是,IL-23R基因rs11465817-rs1343152位点A-A单倍型的中国汉族人具有更高的银屑病发病风险。     

血小板活化因子乙酰水解酶基因Val279Phe突变与银屑病的相关性研究

目的 探讨血小板活化因子乙酰水解酶(PAF-AH)在银屑病发病机制中的作用。方法 等位基因特异性聚合酶链反应技术分析银屑病患者及健康对照者PAF-AH基因Val279Phe位点的多态性,并对含有突变等位基因的多态性片段进行DNA测序分析。采用PAF-AH活性检测试剂盒测定血浆PAF-AH的活性。结果 所有研究对象中发现3例Val279Phe突变型杂合子,未发现突变型纯合子;银屑病组的突变等位基因频率与健康对照组差异无统计学意义(P>0.1);银屑病患者血浆PAF-AH活性低于健康献血者,两组比较差异有统计学意义(P<0.01)。结论 本研究结果提示PAF-AH基因的Val279Phe突变与银屑病无明显的相关关系,可能不是银屑病患者血浆PAF-AH活性降低的主要原因。     

Polymorphisms in interleukin-15 gene on chromosome 4q31.2 are associated with psoriasis vulgaris in Chinese population

Through a series of linkage analyses in a large Chinese family cohort of psoriasis, we previously identified and confirmed a non-HLA psoriasis linkage locus PSORS9 within a small region at 4q31.2-32.1. Within the critical region of the PSORS9 locus, IL-15 has been long recognized as a strong candidate gene for psoriasis. In this study, we investigated the association between IL-15 genetic polymorphisms and psoriasis in a large Chinese sample. Highly significant evidence for association was identified at a single-nucleotide polymorphism (SNP) (g.96516A --> T) within the 3'-untranslated region (UTR) of the IL-15 gene (P=0.00006, after correction for multiple testing). Haplotype analysis using the SNPs within the 3'UTR region also provided strong supporting evidence for association (P=0.00005), where we identified a haplotype of the 3'UTR region of IL-15 associated with increased risk to psoriasis (odds ratio=1.65). This association was also supported by the results of our expression activity analyses, where we demonstrated that the identified risk haplotype is associated with an increased activity of IL-15. Therefore, we provided early evidence for the important role of IL-15 genetic variants in the pathogenesis of psoriasis, probably by increasing interleukin production and inflammation in the lesions of psoriasis.     

Single-point haplotype scores telomeric to human leukocyte antigen-C give a high susceptibility major histocompatibility complex haplotype for psoriasis in a Caucasian population

Psoriasis is a chronic inflammatory skin disease that affects 0.1%-5% depending on the population. PSORS1 is the major susceptibility locus, accounting for approximately 33%-50% of the genetic component of psoriasis among Caucasians. PSORS1 is located within the major histocompatability complex (MHC) locus on 6p21.3. Its position has been refined to hundreds of kilobase and the region located at approximately 100-200 kb telomeric to human leukocyte antigen (HLA)-C is a very strong candidate. To determine the MHC psoriasis risk haplotype, we screened the whole 46 kb interval for single-nucleotide polymorphisms (SNP) and identified 138 SNP. We genotyped 29 SNP throughout this region in psoriatic nuclear families. We calculated the frequency of haplotypes generated by the 29 SNP using all genotyped founder individuals and found four common haplotype with frequency >0.10. We then used SNPtagger to derive the best six SNP and fed these into Transmit using 148 nuclear families. We found that CTGGAC haplotype is a single-point score haplotypes telomeric to HLA-C and gives a 1 df, chi2 of 50.27 (p<0.0001). Most importantly the six selected SNP accurately tagged the most common haplotype found in this region. Moreover, using the same program (Transmit) we show that the association with CTGGAC is higher than the one with HLA-Cw6 (chi2=10.53; p=0.0051). Our results give scores as high as the highest single-point scores suggesting that it is unlikely to be able to discriminate the origin of the association on this analysis on strength of association.