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。     

ANXA6基因多态性与汉族人寻常型银屑病临床表型的相关性

目的:评价汉族人寻常型银屑病ANXA6基因多态性与临床表型的相关性.方法:选取7425例寻常型银屑病患者和11 208例正常对照的ANXA6基因多态性rs999556和rs3762999位点的基因分型资料和临床资料进行分析.结果:病例组与对照组间ANXA6基因多态性rs999556和rs3762999位点的基因型和等位基因分布频率均存在差异(P<0.05);在急性点滴状患者与慢性斑块状患者间,rs999556位点的基因型分布频率存在差异(P<0.05),等位基因分布频率无差异(P>0.05);在儿童期发病与成年发病患者间、有家族史与无家族史患者间,rs999556位点的基因型和等位基因分布频率均无差异(P>0.05).在上述临床表型间,rs3762999位点的基因型和等位基因分布频率均无差异(P>0.05).结论:ANXA6基因多态性rs999556和rs3762999与汉族人寻常型银屑病发病的易感性相关,rs999556与该病的临床类型相关,与发病年龄和家族史不相关;rs3762999与该病的发病年龄、家族史及临床类型均不相关.     

Association of the novel susceptible locus rs9266150 with clinical features of psoriasis vulgaris in the Chinese Han population

Psoriasis is a chronic multifactorial disease and is considered to be strongly associated with the major histocompatibility complex (MHC) region. We have discovered an independent, novel and susceptible psoriasis risk HLA loci, rs9266150; P = 4.52 × 10^?9 for the first time. In this study, we aimed to verify the relationship between the susceptible locus and the subphenotypes of psoriasis vulgaris (PV), including geographic location, gender, age of onset, family history and present skin lesion types (chronic plaque and guttate). To investigate the distribution and association of the rs9266150 gene with clinical phenotypes of PV in Chinese Han population, we conducted an analysis in case‐control and case‐only subjects in the 9906 controls and 8744 cases by MHC targeted sequencing stratified analysis in this study. Significant associations were found with a northern geographic location in the case‐only (P = 1.97 × 10^?4) and the subphenotype‐control analyses (P = 5.57 × 10^?5), males in the case‐only (P = 4.77 × 10^?3) and the subphenotype‐control analyses (P = 7.31 × 10^?4), and guttate psoriasis in the case‐only (P = 4.08 × 10^?3) and the subphenotype‐control analyses (P = 1.27 × 10^?3). There were no significant differences observed between the age of onset (OR = 1.062, 95% CI: 0.9725‐1.16, P = 1.8 × 10^?1) and the family history of psoriasis (OR = 0.981, 95% CI: 0.9048‐1.064, P = 6.43 × 10^?1). The recessive model provided the best fit for rs9266150 (P = 4.38 × 10^?7). Our results implied that rs9266150 might not only play an important role in the development of psoriasis, but also be positively associated with the geographic location, gender and present skin lesion in the Chinese population.     

内质网氨基肽酶1基因rs27044、rs30187和rs26653多态性与汉族寻常性银屑病相关性研究

目的 探讨内质网氨基肽酶1（ERAP1）基因多态性与汉族人寻常性银屑病的遗传关联性。 方法 收集寻常性银屑病患者289例,对照组292例,知情同意后采集外周静脉血5 ml。选择位于ERAP1基因编码区域的3个单核苷酸多态性（SNP）,利用连接酶检测反应进行基因分型（rs27044、rs30187和rs26653）。利用PLINK1.07软件进行统计分析,χ2检验比较患者组与对照组等位基因频率及基因型频率,计算等位基因的相对危险度估计值比值比（OR）及其95%可信区间（95% CI）。利用Haploview软件进行单倍型分析。 结果 rs30187等位基因C及rs26653等位基因G在患者组的频率（分别为0.460 2和0.430 8）、尤其是早发型组中的频率（0.448 5和0.422 7）均明显低于对照组（0.534 2和0.501 7）,差异均有统计学意义（均P < 0.05）。rs27044、rs30187及rs26653这3个SNP两两间均存在强连锁不平衡（r2 ≥ 0.717,D′ ≥ 0.962）。基因型分析结果显示,在隐性遗传模式下,rs30187在患者组及早发型组的基因型频率均显著低于对照组,差异均有统计学意义（P值分别 < 0.05和 < 0.016 7）。单倍型分析发现,单倍型（H4：CTC）在患者组的频率（0.050）、尤其是早发型组的频率（0.052）均明显高于对照组（0.022）,差异均有统计学意义（P值分别 < 0.05、 < 0.016 7）。 结论 ERAP1基因多态性与汉族人寻常性银屑病可能相关,特别是早发型患者。危险单倍型（H4：CTC）可能是寻常性银屑病一个重要的易感因素。     

ADAM33基因多态性与东北汉族银屑病的相关性

目的:确定解整合素金属蛋白酶(ADAM33)基因与东北地区汉族人群银屑病的相关性。方法:利用多重SNaPSHOT方法检测东北汉族400例银屑病患者和398名正常对照的ADAM33基因中rs2787094、rs512625、rs597980位点的基因分型。比较患者和对照组间、不同临床表型组间的基因型、等位基因和单体型频率分布的差异性。结果:ADAM33基因rs2787094CC、CG基因型和2个单体型(H3和H5)可能为银屑病的危险因素(P0.05),rs512625AA基因型和3个单体型(H1、H4和H7)可能是银屑病的保护因素(P0.05)。rs597980的基因型和等位基因在病例和对照组间无差异(P0.05)。rs2787094CC基因型和C等位基因可能与晚期发病和/或无家族史的患者具有相关性,与病情严重程度和性别无关。结论:ADAM33基因的多态位点与东北地区汉族人群银屑病具有相关性。     

HCR基因单核苷酸多态性与维吾尔族银屑病的相关性

目的 探讨HCR基因与银屑病发病的相关性.方法 测定118例新疆维吾尔族寻常性银屑病及127例正常人对照组的HCR基因第4外显子第307位点基因多态性.从抗凝血中抽提DNA,用PCR-RFLP法和PCR产物直接测序法鉴定基因型.对结果进行统计学分析处理.结果 HCR-307位点核苷酸存在C、T二态性,表现为CC纯合、TF纯合、CT杂合三种基因型,病例组TF基因型频率明显高于对照组,差异有统计学意义(P<0.01).结论 HCR-307位点的C→T多态性与新疆维吾尔族寻常性银屑病具有相关性.     

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。     

单核苷酸多态性rs2236313与汉族人寻常型白癜风临床表型的相关性研究

目的:确定染色体6q27区域内一个单核苷酸多态性(single nucleotide polymorphism,SNP)位点rs2236313与汉族人寻常型白癜风临床表型之间的相关性.方法:选取6458例寻常型白癜风患者和9766名正常对照的rs2236313的基因分型资料和临床资料,用χ2检验对各组间基因型和等位基因频率的分布进行比较.结果:rs2236313基因型频率和等位基因频率分布在病例组和对照组间存在统计学差异(P基因型=8.21×10-14,P等位基因=1.26×10-14).在早发和晚发患者、有伴发疾病和无伴发疾病患者之间,rs2236313等位基因频率分布存在统计学差异(P<0.05).在有和无家族史患者、轻与中重度患者之间其分布均无统计学差异(P>0.05).结论:rs2236313与汉族人寻常型白癜风发病易感性相关,且与发病年龄、伴发疾病相关,与家族史、病情严重程度无关.     

Interleukin-12 p40 gene (IL12B) 3'-untranslated region polymorphism is associated with susceptibility to atopic dermatitis and psoriasis vulgaris

Interleukin-12 (IL-12) is believed to play an important role in inducing Th1-type cytokine profiles. Atopic dermatitis (AD) and psoriasis vulgaris (PsV) are considered to be Th2 and Th1 type disease, respectively. The IL-12 p40 subunit gene (IL12B) is located at chromosome 5q31-33 and linkage findings of AD on 5q31 were reported. Recently single nucleotide polymorphism (SNP) (1188A/C) of IL12B has been reported. In function, it has been reported that this SNP is associated with IL12B mRNA expression levels. To learn whether this SNP is associated with susceptibility to AD or PsV, we investigated the genotype and allele frequencies of the SNP in AD patients, in PsV patients and in controls, examining 164 AD patients, 143 PsV patients and 100 healthy individuals in Japanese population. Genotyping was performed using the polymerase chain reaction-restriction fragment length polymorphism method. The A allele was decreased in AD patients (40.9%, p = 0.031) and increased in PsV patients (60.1%, p = 0.035) compared with controls (50.5%). This suggests that IL12B SNP is associated with susceptibility to AD and PsV, presumably by affecting the Th1/Th2 balance.     

寻常型银屑病与载脂蛋白相关性研究

目的探讨我国汉族人寻常型银屑病(PV)与载脂蛋白E(ApoE)等位基因ε2的相关性。方法采用聚合酶链反应限制性长度多态性(PCR-RPLP)方法分析汉族人群中100名健康者和101例PV患者的ApoE基因型,其中,包括Ⅰ型银屑病患者83例,Ⅱ型18例。又按严重程度分为三度(其中轻度31例,中度29例、重度41例)进行探讨。结果在PV组ε3/2基因型和ε2等位基因频率显著高于健康对照组,且ε2等位基因与PV密切关联(RR=2.9096,x2=5.263,P<0.05)。ε3/2基因和ε2等位基因频率还在Ⅰ型银屑病组和中、重度组中分别明显高于Ⅱ型银屑病和轻度组,但无统计学意义。结论:ApoE分子可能在银屑病发病过程中起着重要作用。ε2等位基因可能是PV的-个危险因素,并可能与PV的发病年龄和严重程度有关。PV患者的脂蛋白代谢异常可能是PV病理机制的部分。     

TNIP1基因多态性与中国北方汉族寻常性银屑病关联性分析

目的 探讨人肿瘤坏死因子α诱导蛋白3（TNFAIP3）相互作用蛋白1（TNIP1）基因多态性与中国北方汉族人寻常性银屑病的遗传关联性。 方法 收集寻常性银屑病患者465例,健康对照476例。受试者知情同意后采集外周静脉血5 ml。选择位于TNIP1基因区域的3个单核苷酸多态性（SNP）,即rs17728338、rs3762999和rs999556,利用连接酶检测反应基因分型。利用PLINK1.07软件进行统计分析,卡方检验比较病例组及对照组等位基因频率及基因型频率,计算等位基因的相对危险度估计值比值比OR及其95%可信区间（95% CI）。对 3个SNP间进行连锁不平衡检验,计算两两间的r2和D′值。 结果 位于TNIP1基因区域的3个SNP在病例组和对照组中等位基因频率分布存在差异,但rs3762999和rs999556未达到Bonferroni校正水平。在显性模式下,rs3762999、rs999556的基因型频率在病例组和对照组间差异有统计学意义,达到Bonferroni校正水平（P < 0.016 7）。分层分析发现,3个SNP的等位基因频率、基因型频率在有家族史寻常性银屑病患者与健康对照组间的差异均具有统计学意义（均P < 0.016 7）,rs17728338等位基因A的频率在寻常性银屑病组及各型（早发型、晚发型、有家族史、无家族史）病例组均显著高于对照组（均P < 0.0167）。rs3762999与 rs999556间存在强连锁不平衡（r2 = 0.910,D′ = 0.982）,rs17728338与rs3762999和rs999556之间有中等程度的连锁不平衡（r2分别为0.371和0.353,D′分别为0.989和1）。 结论 TNIP1基因多态性rs17728338、rs3762999及rs999556与汉族人寻常性银屑病具有相关性。     

Association of psoriasis with the VEGF gene polymorphism in the northern Polish population

Background Neovascularization plays an important role in pathogenesis of psoriasis and vascular endothelial growth factor (VEGF) seems to be the main angiogenic factor involved in this disease. Published studies which analysed the role of VEGF gene polymorphism in psoriasis were limited and they received controversial results. Objective The aim of our study was to evaluate the association between ?1154 G/A, ?460 T/C and +405 G/C polymorphisms and the psoriasis susceptibility and to determine whether this genetic variation influence levels of VEGF protein expression. Materials and methods One hundred and eighty‐nine patients with psoriasis and 215 ethnically matched controls were genotyped using ARMS‐PCR and PCR‐RFLP methods. VEGF serum levels were assessed in 47 patients and 40 controls using ELISA test. Results We noted that an increased risk of Type I psoriasis is associated with ?1154 G allele (OR = 1.9; P = 0.04), +405 CC (OR = 2.86; P = 0.03) and ?460 TT (OR = 1.56; P = 0.05) genotypes and demonstrated that a significantly increased risk of developing disease is related to presence of haplotype GTC among all patients (OR = 1.97; P = 0.001), patients with Type I (OR = 1.87; P = 0.005) and Type II psoriasis (OR = 2.37, P = 0.01). We have found significantly increased serum levels of VEGF in patients with psoriasis compared with those in healthy controls (P = 0.008). Serum levels of VEGF significantly correlated with PASI: r = 0.72, P < 0.00001. Patients with elevated levels of VEGF in the serum showed more frequently: GC genotype (P = 0.04), C allele (P = 0.02) at the locus +405 and TT genotype (P = 0.03) at the locus ?460. Conclusion Our results strongly support the role of VEGF gene polymorphism in the pathogenesis of psoriasis.     

HLA-DQA1 and DQB1 alleles are associated with genetic susceptibility to psoriasis vulgaris in Chinese Han

BACKGROUND: Psoriasis vulgaris is a chronic skin disorder characterized by infiltration of inflammatory elements, keratinocyte hyperproliferation and altered differentiation. Although the pathogenesis of psoriasis is not fully understood, there is solid evidence of a susceptibility locus in the human leukocyte antigen (HLA) region. OBJECTIVES: To investigate whether HLA-DQA1 and DQB1 alleles are associated with genetic susceptibility to psoriasis vulgaris in Chinese Han. PATIENTS AND METHODS: The polymerase chain reaction-sequence-specific primer (PCR-SSP) method was used to analyse the distribution of HLA-DQA1 and DQB1 alleles in 189 patients with psoriasis and 273 healthy controls. RESULTS: The HLA-DQA1*0104 (OR = 2.33, P = 0.0001154, Pc = 2.0 x 10-3), DQA1*0201 (OR = 3.36, P < 1.0 x 10-7, Pc < 1.0 x 10-6), DQB1*0201 (OR = 1.64, P = 0.0192, Pc > 0.05) and DQB1*0303 (OR = 1.55, P = 0.0377, Pc > 0.05) alleles were more prevalent in patients with psoriasis vulgaris than in controls, and HLA-DQA1*0501 (OR = 0.30, P = 0.0000039, Pc < 4.0 x 10-5) alleles were less prevalent. The HLA-DQA1*0104 (OR = 2.42, P = 0.0001159, Pc < 2.0 x 10-3), DQA1*0201 (OR = 3.74, P < 1.0 x 10-7, Pc < 1.0 x 10-6) and DQA1*0501 (OR = 0.30, P = 0.0000374, Pc < 4.0 x 10-4) alleles were only associated with type I psoriasis. HLA-DQA1*0104 and DQA1*0201 were more prevalent in patients with or without a family history of psoriasis. However, the DQA1*0501 allele was only more prevalent in patients without a family history of psoriasis. CONCLUSION: HLA-DQA1*0104 and DQA1*0201 alleles may be psoriasis susceptibility genes or may be in close linkage with the susceptibility genes. The HLA-DQA1*0501 allele seems to have a protective effect against the development of psoriasis vulgaris in Chinese Han. There may be a difference in genetic background between psoriasis patients with and without a family history of psoriasis.     

Toll样受体9基因多态性与湖北汉族系统性红斑狼疮易感性的关系

目的：明确Toll样受体9基因rs187084、rs352140位点单核苷酸多态性与湖北汉族人口中系统性红斑狼疮疾病易感性的关系。方法：PCR扩增80例系统性红斑狼疮患者和84例健康志愿者的外周血目的基因片段,通过SNaPshot法检测rs187084、rs352140这两个位点的基因型及等位基因频率。结果：系统性红斑狼疮实验组及健康对照组中rs187084的AA,GG,AG基因型频率分别为37.50%,18.75%,43.75%和47.62%,13.10%,39.29%,无显著统计学差异（P>0.05）。rs352140 AA,GG,AG基因型频率在实验组及对照组中分别为18.75%,43.75%,37.50%和11.90%,48.81%,39.29%,无显著统计学差异（P>0.05）。结论：Toll样受体9的rs187084、rs352140基因位点的单核苷酸多态性可能与系统性红斑狼疮的发病不相关。     

IL-6 and IL-10 promoter gene polymorphisms in psoriasis vulgaris

Overexpression of IL-6 has been implicated in the pathology of numerous autoimmune and chronic inflammatory diseases, including psoriasis, and relative deficiency of IL-10 in psoriatic patients seems to be important in the development of this disease. The aim of this study was to investigate the association between IL-6 and IL-10 single nucleotide polymorphisms and susceptibility to psoriasis vulgaris. DNA from 78 patients with psoriasis vulgaris and 74 healthy volunteers was investigated. IL-6 promoter gene single nucleotide polymorphisms in position -174, and IL-10 single nucleotide polymorphisms in positions -1082, -819 and -592 were evaluated by polymerase chain reaction using sequence-specific primers. No significant differences were found in the polymorphisms of IL-6 and IL-10 promoter genes between patients with psoriasis and healthy controls.     

A single nucleotide polymorphism rs9468925 of MHC region is associated with clinical features of generalized vitiligo in Chinese Han population

Background Vitiligo has been found to be associated with different HLA antigens in different ethnic groups. In our previous genome‐wide association study (GWAS), we identified independent association signal of rs9468925 (P = 2.21 × 10^?33, OR = 0.74) within HLA‐C‐HLA‐B region. Objectives To explore the association between rs9468925 polymorphism within MHC and the clinical features of generalized vitiligo. Methods The study, using 5566 cases and 6462 controls from previous GWA study investigated the single and combined (GA + GG) genotypic distribution of rs9468925 in subsets of vitiligo patients having different clinical features. We performed a QTL analysis (quantitative trait locus) for age of onset with genotype of rs9468925. Results The GA + GG genotypic distribution of SNP rs9468925 tested with an additive model was found to be significantly different in subgroups of patients of >20 vs. <20 years old (genotypic P = 2.57 × 10^?4, combined P = 3.0 × 10^?3, OR = 0.77, 95% CI: 0.64–0.92), and in patients with different clinical subtypes of vitiligo (genotypic P = 0.03, combined P = 5.0 × 10^?3). However, there was no statistical significance for familial history, halo nevi involvement and autoimmune disease involvement. Conclusions Allele G of rs9468925 on HLA‐C‐HLA‐B may be associated with a higher risk of vitiligo. Our study showed a significant genotypic variation between patients with age of onset ≤20 years and age of onset >20 years. Obvious clinical differences of generalized vitiligo related to genotypic variation found in the Chinese Han population were confirmed in this study.     

北方汉族寻常型银屑病与HLA等位基因的关联研究

目的:研究中国北方汉族寻常型银屑病(PsV)与HLA等位基因的关联性。方法:采用序列特异性引物-聚合酶链反应(PCR-SSP)方法检测91例PsV患者和102例健康人HLA-A、B、Cw、DRB1及DQB1等位基因。结果:(1)PsV患者HLA-A*0101-03、A*3001-04、B*5701、Cw*0602、Cw*0603/04/05、DRB1*0701/02及DQB1*0201基因频率较正常对照显著增高;Cw*0401基因频率显著下降(Pc<0.05)。(2)I型PsV患者HLA-A*0101-03、A*3001-04、B*5701、Cw*0602、DRB1*0701/02及DQB1*0201基因频率显著增高,而B*51、Cw*0401、DQB1*0301基因频率显著下降;Cw*0603/04/05基因频率在I型及II型PsV患者均显著增高(Pc<0.05)。有家族史PsV患者HLA-A*3001-04、DRB1*0701/02及DQB1*0201基因频率显著增高;无家族史患者Cw*0602基因频率显著增高,而DQB1*0501-04基因频率显著下降(Pc<0.05)。(3)HLA-A*3001-04、DRB1*0701/02及DQB1*0201基因频率仅在男性PsV患者显著增高;B*5701、Cw*0602基因频率仅在女性患者显著增高(Pc<0.05)。结论:(1)HLA-A*0101-03、A*3001-04、B*5701、Cw*0602、Cw*0603/04/05、DRB1*0701/02及DQB1*0201基因可能是北方汉族PsV的易感基因或与易感基因相连锁。(2)HLA-Cw*0401基因可能是阻止北方汉族PsV发病的“保护因子”。(3)I型或II型、有或无家族史PsV在遗传背景上存在差异。