中国汉族人群染色体1q21存在寻常性银屑病易感基因

目的　确定中国汉族人群染色体1q21上是否存在寻常性银屑病易感基因。方法　用覆盖染色体1q21-1q23.1的8个微卫星标记,对36个寻常性银屑病家系共190个个体（包括92例患者,98例正常人;年龄12 ~ 81岁,平均44岁）进行基因组扫描研究,并用ETDT及GENEHUNTER软件进行连锁不平衡分析。结果　GENEHUNTER示D1S2345与银屑病连锁,其非参数连锁（NPL）值为1.735（P = 0.0329）;扩大范围传递不平衡检验（ETDT）示D1S2346的97 bp等位基因与D1S484的283 bp等位基因分别优先传递给患病子代（P < 0.05）。结论 中国汉族人群染色体1q21区存在寻常性银屑病易感基因。     

染色体4q存在中国汉族人的银屑病易感基因

目的：确定在4号染色体长臂上是否存在中国汉族人寻常性银屑病易感基因。方法：用覆盖4号染色体长臂的12个微卫星标记对64个寻常性银屑病家系共372个个体（包括197例患者和175例非患者）进行基因组扫描研究，并用GENEHUNTER软件（2.0 Version)对基因分型结果进行参数和非参数连锁（NPL）分析。结果：（1）非参数连锁分析：两点连锁分析揭示D4S413和D3S1597的NPL值分别为2．04和2．23，对应的P值分别为0．021和0．014；多点连锁分析在染色体155．1－172．3cM的范围NPL值均大于3，在位点D4S413（157．9cM)处NPL值达最高，为3．44，相应的P值为0．00056。（2）参数连锁分析在显性遗传模式下，外显率10％，基因频率0．0062时在D4S1597位点处得出LOD值＝3．70，异质性LOD（HLOD）值＝4．35和较高的连锁家系比例α=85%。结论：染色体4q存在中国汉族人的寻常性银屑病易感基因。     

6号染色体上可能存在银屑病易感基因

目的 研究中国人寻常型银屑病与6p21.3区域内的六个微卫星标记和4q上的两个微卫星标记是否连锁,以寻找银屑病易感基因位点。方法 利用选取的微卫星位点作为标记,采用微卫星荧光标记-基因扫描及分型技术,选取205例经确诊并符合寻常型银屑病诊断标准的患者,对其中14个银屑病家系进行连锁分析。结果 在研究的家系中未发现4q上的微卫星标记与银屑病易感基因之间的连锁,而在染色体6p21.3区域存在着与之有连锁关系的微卫星标记位点(在D6S273位点上两点分析最大LOD值为1.26)。结论 本研究表明在中国人银屑病患者中,染色体6p21.3区域可能存在银屑病易感基因。     

6号染色体短臂存在银屑病易感基因的证据

目的 鉴定6号染色体短臂上是否存在寻常性银屑病的易感基因.方法用6号染色体短臂上的8个微卫星标记对46个寻常性银屑病家系共272个个体(包括143例患者和129例非患者)进行基因分型研究,并用Genehunter软件(2.0 Version)对基因分型结果进行两点和多点参数和非参数连锁分析.结果①两点连锁分析:非参数连锁分析揭示3个相邻的标记D6S276、D6S1610和D6S1575的NPL值分别为2.69、3.58和2.84,对应的P值分别为0.0 048、0.0 006和0.0 033;参数分析在D6S1610位点处得出HLOD=4.01和较高的连锁家系比例α=70%.②多点连锁分析:在44.9-62.3 cM的染色体区域内,非参数连锁分析的NPL值均＞3,D6S276(44.9 cM)、D6S1610(53.9 cM)和D6S1575(62.3 cM)均位于这个范围内,其中在D6S1610处NPL值达到最高为4.11,对应的P值为0.0 002;参数分析在D6S1610处,得出多点分析的HLOD峰值为3.17,连锁家系比例为60%.结论6号染色体短臂上存在寻常性银屑病的易感基因。     

银屑病家系易感基因定位的研究

目的:探讨银屑病易感基因与第4、6、17号染色体上7个微卫星标记的连锁关系,初步对汉族鲁系银屑病易感基因进行定位研究。方法:选择22个银屑病家系中75例患者和正常人51例。选择7个微卫星标记(STR):D6S276、D6S1610、D4S403、D4S424、D4S415、D17S949、D17S784,利用ABI3730测序仪进行电泳测序,并用与之配套的GeneScan、GeneMapper软件进行基因分型。利用GENEHUNTER软件对STR的基因分型数据进行连锁分析。结果:D17S949、D17S784位点的最大两点LOD值,最大两点NPL值均大于1(P<0.05),提示存在连锁关系。结论:染色体17q23~17q25区域内存在寻常型银屑病易感基因。     

银屑病易感基因位点PSORS1的研究进展

银屑病是一种常见的多基因遗传性皮肤病,通过对不同群体的银屑病患者的基因样本进行全基因组扫描,确定了7个银屑病易感基因位点(PSORS1～PSORSS7),其中位于6p21染色体上的易感基因位点PSORS1是当前银屑病易感基因研究的热点,它包括三个银屑病候选基因:HLA-Cw6,CDSN,HCR.分别对这三个易感基因进行综述.     

银屑病易感基因最新研究进展

随着多基因疾病研究方法的不断进步,银屑病易感基因遗传学研究取得了很大进展。但多基因疾病往往涉及到多个基因的作用,虽然不断发现新的易感位点,但在寻找银屑病易感基因上还没有取得突破。就目前国际上银屑病易感基因的最新研究进展作一综述。     

关节病型银屑病易感基因研究进展

关节病型银屑病(PsA )是一种伴有炎症性关节病变的严重类型银屑病.遗传流行病学研究显示与寻常型银屑病相比,PsA 具有更强的遗传易感性.近期全基因组关联研究发现了IL-12B 、IL-23R、TNF AIP3、TNIP1、IL-13、LCE等多个易感基因位点,揭示了Th17 细胞通路、NFκB通路、Th2 细胞通路、表皮分化通路等在银屑病和PsA发病机制中的作用.     

银屑病易感基因最新研究进展

随着多基因疾病研究方法的不断进步,银屑病易感基因遗传学研究取得了很大进展.但多基因疾病往往涉及到多个基因的作用,虽然不断发现新的易感位点,但在寻找银屑病易感基因上还没有取得突破.就目前国际上银屑病易感基因的最新研究进展作一综述.     

关节炎性银屑病易感基因研究进展

关节炎性银屑病(psoriatic arthritis，PsA)作为一种独立的临床疾病而存在，但因其临床表现多样化及目前对该病尚无统一的定义而增加了对该病研究的困难。除了导致银屑病或关节炎症状的因素之外，PsA可能还存在其独特的易感因素。遗传因素和(或)环境因素可能是其重要病因，该文就近年来关于PsA遗传易感因素的研究作一综述。     

Identification of a locus for dyschromatosis symmetrica hereditaria at chromosome 1q11-1q21

Dyschromatosis symmetrica hereditaria is a rare autosomal dominant cutaneous disorder characterized by a mixture of hyperpigmented and hypopigmented macules of various sizes on the face and the dorsal aspects of the extremities. The genetic basis for this disease is unknown. We performed a genome-wide search in two large Chinese families to map the chromosome location of the responsible gene. We identified a locus at chromosome 1q11-1q21 with a cumulative maximum two-point LOD score of 8.85 at marker D1S2343 (at recombination fraction=0.00). Haplotype analyses indicated that the disease gene is located within the 11.6 cM region between markers D1S2696 and D1S2635. This is the first locus identified for dyschromatosis symmetrica hereditaria. This study provides a map location for isolation of a disease gene causing dyschromatosis symmetrica hereditaria.     

Evidence for a novel psoriasis susceptibility locus at 9q33-9q34 in Chinese Hans

Psoriasis is a heterogeneous disease for which nine linkage loci (PSORS loci 1-5 and PSORS7-10) have been accepted by the Human Genome Nomenclature Committee and an additional 16 potential susceptibility loci have been reported so far. Our previous genome-wide scan in 61 Chinese Han psoriasis vulgaris families found two susceptibility loci at 6p21.3 and 4q31 and additional suggestive linkage evidence at other regions, including 9q33. In this follow-up study, the linkage evidence at 9q33 was further investigated using an expanded sample of 160 families and improved marker coverage. Our follow-up linkage analysis of the 160 families demonstrated strong linkage evidence (P < or = 0.000022) throughout a region between 133.38 and 146.23 cM with a maximum nonparametric linkage (NPL) score of 4.64 (P = 0.00000023) and a heterogeneity LOD (HLOD) score of 5.03 (alpha = 46%) at 142.39 cM near the marker D9S290. By stratifying the 160 families into the subtypes of 130 early-onset and 30 late-onset families, we revealed stronger linkage evidence in the early-onset psoriasis families with a maximum multipoint HLOD score of 6.48 (alpha = 58%) and a maximum NPL score of 4.69 (P = 0.00000012) near marker D9S290. Our follow-up study has confirmed a novel susceptibility locus at 9q33-34 for early-onset psoriasis in the Chinese population.     

Identification of a locus for punctate palmoplantar keratodermas at chromosome 8q24.13-8q24.21

Punctate palmoplantar keratodermas (PPK) is a rare autosomal dominant cutaneous disorder characterized by numerous hyperkeratotic papules that are irregularly distributed on the palms and soles. The genetic basis for this disease is unknown. We performed a genome-wide search in two Chinese families with punctate PPK to map the chromosome location of the responsible gene. We identified a locus at chromosome 8q24.13-8q24.21 with a cumulative maximum two-point LOD score of 5.41 at markers D8S1793 and D8S1774 (at recombination fraction theta=0.00). Haplotype analysis indicated that the disease gene is located within 9.20 cM region between markers D8S1804 and D8S1720. It is the first locus identified for the punctate PPK. This study provides a map location for isolation of a disease gene-causing punctate PPK.     

A new locus for hereditary hypotrichosis simplex maps to chromosome 13q12.12∼12.3 in a Chinese family

Background: Hereditary hypotrichosis simplex (MIM 146520, HHS) is a rare form of nonsyndromic alopecia. The locus for autosomal dominant HHS was mapped to 18p11.32‐p11.23 and 6p21.3, respectively, suggestive of genetic heterogeneity. Aim: To identify the disease‐causing gene for a four‐generation Chinese family with dominant transmission of a form of HHS. The work was carried out at State Key Laboratory of Medical Genomics. Methods: Genome‐wide screening was carried out in a Chinese family with HHS using microsatellite markers, and linkage analysis was performed using the MLINK program. Results: The highest two‐point logarithm of the odds (LOD) score was obtained with the microsatellite marker D13S217 (LOD score of 4.041 at θ = 0.00). After fine mapping and haplotype analysis, we defined a critical region of about 9.57 cM flanked by markers D13S1243 and D13S1299. The disease‐causing gene was mapped to 13q12.12～12.3 in this family. Conclusions: A novel locus for HHS maps to chromosome 13q12.12～12.3 in a Chinese family. Xu C, Zhang L, Chen N, Su B, Pan C‐M, Li J‐Y, Zhang G‐W, Liu Z, Sheng Y, Song H‐D. A new locus for hereditary hypotrichosis simplex maps to chromosome 13q12.12～12.3 in a Chinese family.     

Identification of a locus for disseminated superficial actinic porokeratosis at chromosome 12q23.2-24.1

Disseminated superficial actinic porokeratosis is an autosomal dominant cutaneous disorder characterized by many uniformly small, minimal, annular, anhidrotic, and keratotic lesions. The genetic basis for this disease is unknown. Using a genomewide search in a large Chinese family, we identified a locus at chromosome 12q23.2-24. 1 responsible for disseminated superficial actinic porokeratosis. The fine mapping study indicates that the disseminated superficial actinic porokeratosis gene is located within a 9.6 cM region between markers D12S1727 and D12S1605, with a maximum two-point LOD score of 20.53 (theta = 0.00) at D12S78. This is the first locus identified for a genetic disease where the major phenotype is porokeratosis. The study provides a map location for isolation of a gene causing disseminated superficial actinic porokeratosis.     

Evidence for a major psoriasis susceptibility locus at 6p21(PSORS1) and a novel candidate region at 4q31 by genome-wide scan in Chinese hans

Psoriasis is a heterogeneous disease with seven major psoriasis susceptibility loci reported so far on chromosomes 1p, 1q, 3q, 4q, 6p, 17q, and 19p, respectively. To investigate the psoriasis susceptibility loci in Chinese Hans, a genome-wide scan was performed with two-point and multipoint parametric and nonparametric linkage analyses in 61 multiplex families. These families were Chinese Hans residing in east and south-east China, comprising 189 affected and 166 unaffected individuals. We detected evidence for linkage at 6p21 (PSORS1) with nonparametric linkage scores > 3 in the range of 39.9-62.3 cM and a maximum multipoint nonparametric linkage score of 4.58 (p=0.000032). Parametric analysis revealed a maximum two-point heterogeneity lod score of 4.30 with 58% as the proportion of linked families (alpha) and a maximum multipoint heterogeneity lod score of 4.25 (alpha=53%) under the assumption of a dominant model. We could not confirm a previous reported locus (PSORS3) on distal chromosome 4q; however, a region of highly suggestive linkage was identified proximal to this proposed locus. Multipoint nonparametric analysis demonstrated nonparametric linkage scores > 3 throughout a region between 152.5 cM and 165.1 cM (from pter) with a maximum peak of 3.69 (p=0.00033) at 157.9 cM, which locates D4S413. A maximum multipoint heterogeneity lod score of 2.31 (alpha=46%) was reached at 163.1 cM. With two-point parametric linkage analysis, we observed the highest lod score of 2.43 and heterogeneity lod score of 3.94 (alpha=77%) at marker D4S1597. Our results showed that chromosomes 6p and 4q may contain genes involved in the susceptibility to psoriasis vulgaris in a Chinese Han population. Other regions with weaker evidence for linkage could also hide minor susceptibility genes.     

关节病型银屑病与HLA-DRB1等位基因相关性研究

目的:探讨HLA-DRB1等位基因与山东汉族关节病型银屑病(PsA)及其临床类型的相关性.方法:应用聚合酶链反应-寡核苷酸探针杂交分型法(PCR-SSOP)对42例山东汉族PsA(病例组)与90例健康献血者(对照组)进行HLA-DRB1等位基因分型.结果:42例PsA患者组中共检测到13对HLA-DRB1等位基因,未发现与PsA及其临床类型相关的HLA-DRB1等位基因,DRB1*12(P=0.036)等位基因出现的频率明显低于对照组,但经校正后无显著性差异.结论:HLA-DRB1等位基因可能与山东汉族PsA及其临床类型无关,对PsA的分型及预后价值有限.     

Suggestive linkage of familial primary cutaneous amyloidosis to a locus on chromosome 1q23

BACKGROUND: Large or deteriorated skin defects are sometimes life threatening. There is increasing evidence that adult stem cells are useful for tissue regeneration. Human mesenchymal stem cells (hMSCs) are self-renewing and are potent in differentiating into multiple cells and tissues. OBJECTIVES: To investigate the effects of hMSCs in cutaneous wound healing. METHODS: Wound healing was studied in an hMSC-populated porcine skin substitute, using a nude rat model to minimize immune reactions. Full-thickness skin and soft tissue defects of 1.5 x 1.5 cm in size, including the panniculus carnosus, were excised and covered with hMSCs and basic fibroblast growth factor (bFGF)-soaked skin substitutes and an evaluation was made of wound size, histology and protein expression at 3, 7 and 42 days after injury. RESULTS: The wound size was significantly smaller in the hMSC-treated groups (P < 0.01) and any dose of bFGF (1, 10, 100 microg) enhanced the healing (P < 0.01). The re-epithelialization markers integrin alpha3 and skin-derived antileucoproteinase were remarkably increased with the presence of bFGF in a dose-dependent manner, while the mesenchymal cell surface markers CD29 and CD44 were downregulated in a time-dependent manner. Human pancytokeratin, which does not cross-react with rat antigens, was observed by Western blotting at 38 kDa and 42 kDa from the hMSC-treated tissues on day 7. The expression levels were elevated by 10 microg bFGF (P < 0.01). The immunohistochemical expression of human pancytokeratin was only observed in the hMSC-treated groups. CONCLUSIONS: These data suggest that hMSCs together with bFGF in a skin defect model accelerate cutaneous wound healing as the hMSCs transdifferentiate into the epithelium.     

Analysis of chromosome 5q31-32 and psoriasis: confirmation of a susceptibility locus but no association with SNPs within SLC22A4 and SLC22A5

We have previously reported a region on chromosome 5q as a possible susceptibility region for psoriasis. This cytokine cluster-rich region has also been suggested as a susceptibility locus in other autoimmune or inflammatory diseases including Crohn's disease (CD) and rheumatoid arthritis (RA). Three specific single-nucleotide polymorphisms (SNPs) have been reported to associate with RA and CD and to change the functional activity of two organic cation transporters, solute carrier family 22 member 4/5 (SLC22A4) and (SLC22A5). In this study, we have analyzed these SNPs for an association with psoriasis. We have also performed a denser linkage analysis of this region with an additional 31 microsatellite markers. We were not able to detect any association with any of the three SNPs analyzed. However, our linkage result supports the involvement of this region in the etiology of psoriasis. We obtained a peak non-parametric linkage value of 3.1 for marker D5S436 in a subgroup of patients with joint complaints. This result supports the findings in another study of psoriasis patients originating from Iceland in which the authors obtained a peak logarithm of the odds score of 2.6 for marker D5S2090, only 2 Mb from D5S436. This suggests a psoriasis susceptibility locus on chromosome 5q32 that is involved in the arthritic phenotype of the disease.