新疆维吾尔族HCR基因多态性与寻常性银屑病的相关性研究

目的 检测新疆维吾尔族寻常性银屑病(PsV)患者外周血DNA中HCR基因第16外显子的1911位点多态性,探讨其与银屑病发病的相关性。方法 从128例患者及健康对照组132例的抗凝血中提取DNA,用PCR-限制性片段长度多态性法及PCR产物直接测序法鉴定基因类型,对结果进行统计学分析处理。结果 HCR基因第16外显子的1911位点核苷酸存在G、A二态性,可表现为GG纯合、AA纯合、GA杂合三种基因型。基因型和等位基因频率经卡方检验两组比较,差异无统计学意义(P>0.05)。其中Ⅰ型、Ⅱ型寻常性银屑病患者与对照组比较,差异无统计学意义(P>0.05),男女寻常性银屑病患者与对照组比较,差异无统计学意义(P>0.05)。结论 HCR基因第16外显子1911位点的多态性与新疆维吾尔族非家系寻常性银屑病在基因型和等位基因频率方面未发现相关性。     

HCR-325多态性与汉族人寻常性银屑病的相关性

目的探讨HCR基因与银屑病发病的相关性。方法从抗凝血中抽提基因组DNA,用PCP-RFLP法检测HCR基因第4外显子325位点多态性。结果HCR-325位点核苷酸存在C,T多态性,表现为CC纯合、TT纯合、CT杂合三种基因型,病例组T等位基因频率明显高于对照组,差异有统计学意义(P<0.05)。结论HCR-325位点的C→T多态性与汉族人群寻常性银屑病具有一定的相关性。     

CTLA-4基因启动子区域多态性与寻常型银屑病的相关性

目的: 探讨CTLA-4基因启动子区-1722位点(T/C)多态性和-1661位点(A/G)多态性与中国汉族人群寻常型银屑病的相关性.方法: 采用聚合酶链反应(PCR)-限制性片段长度多态性(RFLP)方法,对87例寻常型银屑病和116例中国汉族正常对照者进行CILA-4基因-1722位点和-1661位点多态性检测.结果: 与正常对照组比较,银屑病患者CTLA-4基因-1661位点A/G+G/G基因型频率显著升高(P=0.003);G等位基因基因型频率显著升高(P=0.002);G等位基因携带者也是明显高于对照组(P=0.003).结论: CTLA-4基因启动子区-1661位点G等位基因与中国汉族寻常型银屑病显著相关.     

新疆汉族SPRR2E基因单核苷酸多态性与寻常性银屑病的关系

目的通过测定中国新疆汉族非家系寻常性银屑病SPRR2E基因的外显子编码区序列,研究SPRR2E基因与新疆汉族银屑病发病的关系。方法从新疆汉族正常人和寻常性银屑病患者的外周血中提取基因组DNA,用自动测序的方法测定SPRR2E基因的外显子编码区序列,对结果进行统计学分析处理。结果SPRR2E基因编码区第156核苷酸(+156bp)处存在A或G二态性,可表现为AA纯合、GG纯合和AG杂合三种基因型,病例组AA基因型频率明显高于对照组,差异有统计学意义(P<0.05)。结论SPRR2E基因外显子编码区序列的第156核苷酸多态性与新疆汉族非家系寻常性银屑病的发病有关。     

E选择素基因多态性与广西壮族系统性红斑狼疮的相关性研究

目的 探讨E选择素基因第2外显子G98T和第4外显子A561C多态性在广西壮族人群中的分布及其与系统性红斑狼疮(SLE)的相关性。方法 用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术检测82例系统性红斑狼疮患者和95例正常对照者E选择素基因型。结果 E选择素第2外显子基因型GG、GT、TT频率在SLE组和对照组分别为86.6%、12.2%、1.2%和90.5%、8.4%、1.1%;E选择素第4外显子基因型AA、AC、CC频率在SLE组和对照组分别为81.7%、15.9%、2.4%和92.6%、7.4%、0.0%。E选择素第4外显子基因型频率和等位基因频率在SLE组和对照组比较差异均有统计学意义(P<0.05)。基因型频率的相对风险分析发现,AC+CC基因型患SLE的风险是AA基因型2.81倍(OR=2.81,95%CI为1.087～7.290)。结论 E选择素A561C基因多态性与广西壮族人群SLE的发病有相关性,C等位基因可能是SLE的易感基因。     

白介素10基因启动子多态性与广西壮族系统性红斑狼疮的关系

目的 探讨广西壮族人白介素10(IL-10)基因启动子区单核苷酸多态性与广西壮族SLE的关系.方法 采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术,检测90例SLE患者和110例正常对照者IL-10基因启动子-1082A/G、-819T/C和-592A/C位点基因型.结果 IL-10基因-819T/C和-592A/C多态性在SLE组和正常人群中的分布差异无统计学意义(P>0.05),而IL-10基因-1082A/G多态性在两组人群中的分布差异有统计学意义(P<0.05),基因型频率的相对风险分析发现,AG基因型携带者患SLE的风险是AA基因型的2.076倍(OR=2.076,95%CI:1.052～4.100);基因单倍型分析发现,GCC单倍型携带者显著增加了SLE的发病风险.结论 白介素10基因启动子-1082A/G多态性和它的单倍型与SLE具有相关性,其中-1082G等位基因可能是SLE的遗传易感基因.     

系统性红斑狼疮与亚甲基四氢叶酸还原酶基因多态性的相关性

目的 探讨亚甲基四氢叶酸还原酶(MTHFR)基因第四外显子第677位C→T突变与系统性红斑狼疮(SLE)的相关性。方法 检测40例SLE患者和20例正常人对照组血浆同型半胱氨酸水平,用聚合酶链反应(PCR)-限制性片段长度多态性法作MTHFR基因分型。结果 SLE患者组血浆同型半胱氨酸水平明显高于正常人对照组.而活动期SLE患者与非活动期SLE患者之间血浆同型半胱氨酸水平差异无统计学意义。SLE患者组MTHFR基因TT型占62.5%,明显高于其他两种基因型和正常人对照组(15%)。MTHFR基因677位发生C→T突变可导致血浆同型半胱氨酸水平明显升高,且TT型的效应要明显强于CT型的效应。结论 MTHFR基因多态性是影响SLE患者同型半胱氨酸水平的主要因素之一。MTHFR基因第677位TT型是SLE的易感基因或与易感基因紧密连锁。     

汉族寻常性银屑病患者IFN-γ受体2基因多态性研究

目的 探讨IFN-γ受体2(IFN-γR2)基因氨基酸位点Gln64Arg多态性与中国汉族寻常性银屑病的相关性.方法 采用PCR-限制性片段长度多态性(RFLP)方法及DNA测序方法,检测苏皖地区182例汉族寻常性银屑病患者和114例正常人对照IFN-γR2基因Gln64Arg位点多态性.结果 寻常性银屑病患者与正常人对照组IFN-γR2基因Gln64Arg多态性位点各基因型及等位基因频率分布差异无统计学意义(P>0.05).伴甲损害银屑病组与无甲损害银屑病组之间Gln64/Gln64基因型分布频率分别为57.5%和38.1%.差异有统计学意义(X~3=5.33,P=0.02);Arg4等位基因(Gin64等位基因)分布频率分别为19.3%(80.7%)和30%(70%),差异也有统计学意义(X~2=5.03,P=0.02).伴甲损害的银屑病患者组Gln64/Arg64基因型分布频率为29.8%,正常人对照组为49.1%,两组间分布差异有统计学意义(X~2=5.48,P=0.01);Gln64/Gln64基因型分布频率在两组间分别为57.5%和35.1%,差异有统计学意义(X~2=6.23,P=0.01);无甲损害组与正常人对照组之间差异则无统计学意义.在以上呼吸道感染为诱因或加重因素的银屑病组与非上呼吸道感染银屑病组之间Arg64/Arg64基凶型分布频率分别为33.3%和15.5%,差异有统计学意义(X~2=4.94,P=0.03);Arg64等位基因(Gin64等位基因)分布频率为51.9%(48.1%)和35.2%(64.8%),差异也有统计学意义(X~2=5.46,P=0.02).结论 IFN-γR2基因Gln64Arg多态性位点可能与寻常性银屑病患者是否伴有甲损害有关,也可能与以上呼吸道感染为诱因或加重因素的寻常性银屑病有关.     

银屑病患者亚甲基四氢叶酸还原酶基因C677T多态性及与MTX疗效、毒副作用的关系

目的:确定亚甲基四氢叶酸还原酶(MTHFB)基因C677T多态性与银屑病患者的关系.方法:对108例银屑病患者和102名正常对照个体采用PCR- RFLP方法检测C677T位点基因型,分析银屑病患者基因型分布与正常对照者的差异.分析62例接受甲氨蝶呤(MTX)治疗的不同基因型银屑病患者的临床疗效及毒副作用.结果:银屑病患者MTHFRC677位点T等位基因频率为28.7％,C等位基因频率为71.3％,对照组T等位基因频率为35.78％,C等位基因频率为64.22％,两组间无统计学差异.62例接受MTX治疗的患者中61例有效,TT基因型患者组MTX治疗毒副作用的发生率为55.56％,高于CC基因型(24.24％)和CT基因型(25％),有统计学差异(P=0.04).结论:MTHFR基因C677T多态位点与银屑病的易感性无相关,MTHFR的TT基因型与MTX不良反应作用可能相关.     

白介素12B基因rs6887695多态性与汉族人寻常性银屑病临床表型的相关性

目的 探讨白介素12B（IL-12B）基因多态性位点rs6887695与汉族人寻常性银屑病临床表型（发病年龄、家族史、临床类型、性别）的相关性。 方法　采用ABI Taqman探针荧光PCR技术,对575例寻常性银屑病患者和1403例健康对照的DNA样本进行IL-12B基因多态位点rs6887695的基因分型。使用SPSS14.0分析软件,χ2检验比较患者组和健康对照组间、不同临床表型组间的基因型和等位基因频率分布的差异性。 结果 IL-12B基因多态性位点rs6887695三种基因型（GG、GC、CC）频率在寻常性银屑病患者组分别为42.61%、45.39%和12.0%,健康对照组分别为34.42%、47.83%和17.75%;等位基因频率（G、C）患者组分别为65.30%和34.70%,健康对照组分别为58.34%和41.66%,基因型和等位基因频率分布在患者组和健康对照组间差异均有统计学意义（χ2值分别为16.31和16.54,P值均 < 0.01）,在慢性斑块状（543例）和急性滴状银屑病患者（32例）组间的差异均有统计学意义（χ2值分别为18.11和12.19,P值均 < 0.01）。等位基因G和基因型GG在患者组中的频率明显高于健康对照组,等位基因G和基因型GG在斑块状患者中的频率高于滴状患者。少儿发病组（35例）与成人发病组（540例）、家族史阳性组（102例）与家族史阴性组（440例）、男性患者组（341例）与女性患者组（234例）的基因型和等位基因频率分布差异均无统计学意义（P值均 > 0.05）。 结论 IL-12B（rs6887695）基因多态性与汉族人寻常性银屑病易感性相关联,特别是与斑块状银屑病相关,但与患者的发病年龄、家族史及性别可能无关联。     

SPRR2E基因编码区单核苷酸多态性与银屑病

目的通过测定32个中国汉族人寻常性银屑病家系共157人SPRR2E基因的外显子编码区序列,研究SPRR2E基因与银屑病发病的关系。方法提取基因组DNA,对32个银屑病家系DNA进行扩增,产物经377DNA测序电泳仪电泳,用自动测序的方法测定SPRR2E基因的外显子编码区序列,并以ETDT及GENEHUNTER软件进行统计处理。结果SPRR2E基因编码区第156核苷酸( 156bp)处存在A或G二态性,可表现为AA纯合、GG纯合和AG杂合三种基因型,虽然该SNP不改变蛋白质编码,但它与银屑病存在传递不平衡,等位基因A优先传递给患病子代(P<0.05)。结论SPRR2E基因的外显子编码区中的一个核苷酸多态性与中国汉族人寻常性银屑病的发病相关联。     

Psoriasis vulgaris in Chinese individuals is associated with PSORS1C3 and CDSN genes

BACKGROUND: Besides the HLA-Cw*0602 allele, the psoriasis susceptibility 1 candidate 3 (PSORS1C3) and corneodesmosin (CDSN) genes are two probable psoriasis susceptibility genes in the PSORS1 locus. The -79C, -26C and +246A alleles of the PSORS1C3 gene, the CDSN*971T allele, CDSN*TTC (619T-1236T-1243C) and CDSN*5 (619T-1240G-1243C) are strongly associated with psoriasis in the caucasian population. Until now, no haplotype study of the PSORS1C3 and CDSN genes has been documented in Chinese patients with psoriasis vulgaris. OBJECTIVES: We aimed to determine whether genetic polymorphisms of the PSORS1C3 and CDSN genes were associated with an increased risk of psoriasis vulgaris in Chinese patients in Taiwan. METHODS: We investigated the PSORS1C3 and CDSN genes for disease association by direct sequencing in 178 patients with psoriasis vulgaris and 203 control subjects. Genotyping for HLA-Cw*0602, alpha-helix coiled-coil rod homologue (HCR) gene and single nucleotide polymorphism (SNP) n.9 was also carried out using a sequence-based typing method. RESULTS: The PSORS1C3*582A allele, an SNP in the 3'-untranslated region of the PSORS1C3 gene, was a major psoriasis vulgaris susceptibility allele in the Chinese population, and the association was much stronger in patients with early-onset psoriasis vulgaris (22.3% vs. 6.9%, odds ratio = 3.87, P(c) =0.0000072). The frequencies of CDSN*TTC and CDSN*971T were also significantly increased in patients with early-onset psoriasis vulgaris. Moreover, PSORS1C3*582A, SNP n.9*C, Cw*0602 and HCR*WWCC were in near complete linkage disequilibrium (LD) with each other; in contrast, the LD with the CDSN gene was not so strong. SNP n.9*C-Cw*0602-PSORS1C3*582A-HCR*WWCC was a major susceptibility haplotype in patients with early-onset psoriasis vulgaris (P < 10(-7)) and this risk haplotype also carried CDSN*TTC and CDSN*971T. CONCLUSIONS: The PSORS1C3 and CDSN genes are important psoriasis susceptibility genes in Chinese patients with psoriasis vulgaris.     

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.     

The HCR gene on 6p21 is unlikely to be a psoriasis susceptibility gene

The PSORS1 locus in the human major histocompatibility complex on 6p21 has been consistently associated with psoriasis in populations of diverse ethnicity. The HLA-C allele Cw*0602, located therein, has been found in up to 67% of psoriasis patients but is no longer considered a candidate gene in itself. The alpha-helix coiled-coil rod homolog gene (HCR, previously Pg8) is located 110 kb from the HLA-C gene, positioned between the CDSN and SC1 genes, within a region thought to harbor a psoriasis gene (PSORS1). We investigated the HCR gene for disease association by direct sequencing of nine polymerase chain reaction products amplified from a series of Swedish psoriasis patients and controls. We found that HCR is a very polymorphic gene with 25 polymorphisms in the open reading frame alone, of which 10 demonstrated disease association; however, the relationship between HCR polymorphisms and HLA-Cw*0602 indicates that HCR cannot truly be considered a likely candidate gene. We investigated Cw*0602 association while stratifying for HCR single nucleotide polymorphisms. We also investigated HCR single nucleotide polymorphism association with the disease while stratifying for the presence of Cw*0602. We found that whichever single nucleotide polymorphism that was stratified for, there was still a strongly significant Cw*0602 association with psoriasis; however, when we stratified for Cw*0602 presence, only one silent polymorphism showed significant association. In a recent similar study this polymorphism was actually found to be decreased in psoriasis individuals. Thus we conclude that HCR polymorphisms display association with psoriasis due to linkage disequilibrium with Cw*0602 and is, therefore, unlikely to be directly involved in the development of psoriasis.     

寻常性银屑病患者与正常人SPRRs基因的研究

目的　探讨SPRRs基因的外显子编码区序列与银屑病发病的关系。方法　从正常人和寻常性银屑病患者的外周血中提取基因组DNA ,用自动测序的方法测定SPRRs基因的外显子编码区序列。结果　正常人和银屑病患者的SPRR2A ,SPRR2B及SPRR2D基因外显子编码区序列均相同 ;SPRR2EcDNA在 +15 6bp处存在A或G二态性 ,可表现为AA纯合、GG纯合和AG杂合三种基因型 ,但不改变蛋白质编码 ,其分布在银屑病患者和正常人之间差异无显著性。结论　SPRRs基因的外显子编码区序列与寻常性银屑病的发病无明显相关性