The association of polymorphisms of the vitamin D receptor gene with psoriasis in the Han population of northeastern China

BackgroundThe vitamin D receptor (VDR) is a master regulator of epidermal barrier function, inflammation, stem-cell proliferation, and microbial defense.ObjectiveTo evaluate the association between the VDR and psoriasis in the northeastern Chinese Han population.MethodsIn this case–control study, 342 patients with psoriasis and 341 controls were genotyped for five common VDR gene polymorphisms (ApaI, TaqI, BsmI, FokI, and Cdx2) by the Multiplex SNapSHOT method.ResultsThe frequency of ApaI (rs7975232) allele A was significantly increased in psoriasis relative to the control group (27.8% vs. 22.1%, p = 0.018); the allele A of the ApaI polymorphism showed a 1.35-fold increased risk of developing psoriasis. Haplotype analyses showed the BsmI/ApaI/TaqI/Cdx2/FokI GATGC to be significantly over-represented in psoriasis patients compared with controls (p = 0.012). The BsmI/ApaI/TaqI haplotype GCT was presented to a lesser extent in psoriasis patients in comparison with control patients (72.2% vs. 77.9%, p = 0.012).ConclusionsThese data suggest that VDR polymorphisms are associated with psoriasis in Northeastern Han Chinese population.     

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。     

山东汉族寻常性银屑病患者eIF4E、MMP-9基因多态性研究

目的 探讨真核细胞翻译起始因子（eIF4E ）、基质金属蛋白酶-9（MMP-9）基因内的单核苷酸多态性与山东汉族寻常性银屑病的关系。方法 基于群体的病例对照关联分析方法,利用Taqman分型方法对188例银屑病患者及280例正常对照人群MMP-9基因内的2个位点以及eIF4E基因内的1个位点进行分析,对基因型频率及等位基因频率采用PLINK软件进行统计学分析。结果 位于MMP-9基因上游调控区域的 rs4810482等位基因T在银屑病组中的频率显著低于对照组（OR = 1.49,95% CI = 1.12 ~ 1.99,P < 0.01）,在隐性与显性遗传模型分析中,差异具有统计学意义。生物信息学分析表明,该位点可能改变了转录因子的结合位点。在研究中分析的其余两个位点rs3918254和rs11723037与银屑病无相关性。结论 位于MMP-9基因上游调控区域的rs4810482与银屑病具有显著相关性,可能是银屑病的一个易感基因。     

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。     

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。     

TNIP1基因多态性与汉族人系统性红斑狼疮相关性研究

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）基因多态性与汉族人系统性红斑狼疮（SLE）的遗传关联性。 方法 收集284例汉族人SLE和630例汉族人对照,选择TNIP1基因区域120个单核苷酸多态性（SNP）,利用连接酶检测反应（LDR）对其进行基因分型,对分型数据利用PLINK 1.07和Haploview软件进行统计分析。 结果 经过数据质控,最终105个SNP的分型数据进入最终统计分析。rs3805433 C、rs12516176 C、rs6869605 C和rs4958882 G的等位基因频率在SLE组（参考等位基因频率0.301 ~ 0.306）高于对照组（参考等位基因频率0.221 ~ 0.225）,差异有统计学意义（OR：1.50 ~ 1.53,均P < 4.72 × 10-4）。这4个SNP间存在强连锁不平衡（r2 ≥ 0.871,D′ ≥ 0.938）,且与既往报道的SLE相关SNP rs10036748间存在中等程度的连锁不平衡（r2 ≥ 0.073,D′ ≥ 0.868）。单倍型分析发现,单倍型（H2：CCCGT）在病例组中的频率（0.290）显著高于对照组（0.210）,差异有统计学意义（OR = 1.54,P < 4.72 × 10-4）。 结论 TNIP1基因多态性与汉族人SLE具有相关性。     

山东汉族麻风病与HLA-I类抗原等位基因的相关性研究

目的:分析HLA-I类抗原与麻风病的相关性.方法:应用LifeMatch DNA试剂盒,PCR扩增,Luminex100流式分析仪(PCR-SSOP原理)检测山东地区汉族116例麻风患者和117例健康对照HLA-A,B等位基因.采用χ2检验比较患者组和对照组间基因频率的差异.结果:HLA-A24出现频率高于正常对照组,HLA-B46、B50、B57、B58、B67在患者组中出现频率明显低于正常对照组,但无统计学意义.结论:HLA-A、B等位基因与山东汉族麻风无明显相关性.     

Associations of promoter region polymorphisms in the tumour necrosis factor-alpha gene and early-onset psoriasis vulgaris in a northern Polish population

BACKGROUND: Tumour necrosis factor (TNF)-alpha is considered to be an important mediator in the pathogenesis of psoriasis. Increased levels and activity of this cytokine have been observed in blood and skin of patients with psoriasis. As certain allelic variants of the TNF-alpha gene are associated with increased or decreased production of TNF-alpha, the disturbed cytokine balance may be under genetic control. OBJECTIVES: To investigate the potential association of TNF-alpha promoter alleles within subtypes of psoriasis compared with healthy controls in a northern Polish population. METHODS: We analysed 166 patients with psoriasis vulgaris (134 with type I and 32 with type II) and 65 healthy controls. The polymorphisms -238G/A and -308G/A in the promoter region of the TNF-alpha gene were typed using the amplification refractory mutation system-polymerase chain reaction method. RESULTS: We found that the TNF-alpha-308A allele frequency was significantly decreased among patients with early-onset psoriasis in comparison with control subjects (7.5% vs. 15.4%, P = 0.022), whereas in the same patients the frequency of the TNF-alpha-238A allele was significantly increased as compared with the controls (16.8% vs. 3.1%, P = 0.000017, odds ratio 8.79, 95% confidence interval 2.606-29.678). Patients with early-onset psoriasis with -238 genotype GA or AA were found more often among those with age at onset < 25 years in comparison with those with genotype GG (31.7% vs. 9.1%, P = 0.0312). We also found that the mean +/- SD age at onset among -238A carriers was significantly lower in comparison with that associated with the -238GG genotype (13.5 +/- 7.4 vs. 19.2 +/- 9.9 years, P = 0.0132). CONCLUSIONS: Our study confirming the association between -238 G/A TNF-alpha promoter polymorphism and early-onset psoriasis vulgaris in the northern Polish population suggests that the -238A variant may contribute not only to a predisposition to psoriasis vulgaris but also to the disease phenotype.     

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.     

兰州地区汉族寻常型、关节病型银屑病与HLA-DQB1*0201相关性研究

目的:分析兰州地区汉族寻常型、关节病型银屑病与HLA-DQB1*0201等位基因的相关性.方法:采用聚合酶链反应-序列特异引物(polymerase chain reaction sequence specific primers, PCR-SSP)法检测41例寻常型银屑病患者、27例关节病型银屑病患者和52名健康对照的等位基因频率.结果:寻常型银屑病患者组HLA-DQB1*0201等位基因频率较正常对照组显著增高;关节病型银屑病患者组HLA-DQB1*0201等位基因频率较正常对照组显著增高.结论:HLA-DQB1*0201等位基因可能是兰州地区汉族寻常型、关节病型银屑病的遗传标志.     

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.     

HLA-DRB1，DQA1，DQB1基因单倍型与华东地区汉族人群白癜风的相关性

目的 探讨HLA-DRB1、DQA1、DQB1基因单倍型与华东地区汉族人群白癜风的相关性。方法 采用聚合酶链反应-序列特异性寡核苷酸探针(PCR-SSOP)方法检测华东地区汉族白癜风患者HLA-DRB1、DQA1、DQB1位点的等位基因,运用遗传学群体与家系资料计算机分析系统3.0筛选并分析单倍型。结果 与正常人对照组比较,HLA-DRB1^*09-DQA1^*03-DQB1^*0303单倍型频率显著增高(Pc=0.02,OR=2.542)。结论 在华东地区汉族人群中,HLA-DRB1^*09-DQA1^*03-DQB1^*0303单倍型可能是白癜风的易感单倍型。     

Association of apolipoprotein allele ε2 with psoriasis vulgaris in Japanese population

Received: 7 October 1996     

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。     

山东汉族梅毒患者与HLA-A、B等位基因的相关性研究

目的 探讨山东汉族梅毒患者与HLA-A、B等位基因的相关性.方法 采用PCR-序列特异性寡核苷酸探针杂交(PCR-SSOP)方法对205例山东汉族梅毒患者与5844例山东汉族正常对照的HLA-A、B等位基因表现频率进行检测.结果 梅毒患者组HLA-A*02,B*15、40等位基因频率高于对照组(P值均＜0.01;Pc值均＜0.05),HLA-A*26等位基因频率低于对照组(P=0.003;Pc=0.039),HLA-B*15、40等位基因频率在显性梅毒组高于对照组(P值均＜0.01;Pc值均＜0.05),HLA-A*02、11、29,B*15、40等位基因频率在隐性梅毒组高于对照组(P值均＜0.01;Pc值均＜0.05),HLA-A*30、33等位基因频率在隐性梅毒组低于对照组(P值、Pc值分别为0.002、0.026;0.001、0.013),HLA-A*30等位基因频率在显性梅毒组高于隐性梅毒组(P=0.001;Pc=0.013).结论 HLA-A*02,B*15、40等位基因可能与山东汉族梅毒相关,HLA-A*30可能与山东汉族显性梅毒相关,HLA-A*02、11、29可能与山东汉族隐性梅毒相关.

Abstract：

Objective To investigate the association of HLA-A and -B alleles with syphilis in Shandong Han population. Methods The allele frequencies of HLA-A and -B were detected in 205 patients with syphilis and 5844 normal human controls by PCR-sequence specific oligonucleotide probe (PCR-SSOP)method. Results The patients with syphilis showed a higher frequency of HLA-A*02, B*15, B*40 alleles(all P＜0.01, Pc＜0.05) and a lower frequency of HLA-A*26 allele (P= 0.003, Pc = 0.039) than the normal human controls did. There was an increased frequency of HLA-B*15 and B*40 alleles in patients with symptomatic syphilis (both P＜0.01, Pc＜0.05), as well as an elevated frequency of HLA-A*02, 11, 29, B*15 and 40 alleles (all P＜0.01, Pc＜0.05) and a decreased frequency of HLA-A*30 and 33 in patients with asymptomatic syphilis(P=0.002, 0.026, Pc=0.001, 0.013 respectively), compared with the normal human controls. The frequency of HLA-A*30 allele was significantly higher in patients with symptomatic syphilis than in those with asymptomatic syphilis (P = 0.001, Pc = 0.013). Conclusions There seems to be an association between HLA-A*02, B* 15 and B*40 alleles and syphilis, between HLA-A*30 allele and symptomic syphilis, and between HLA-A*02, 11 and 29 alleles and asymptom1atic syphilis, in Shandong Han population.     

Association of IL-12B gene rs6887695 polymorphism with hereditary susceptibility and clinical characterization of psoriasis vulgaris in the Chinese Han population

We aimed to investigate the role of IL-12B gene polymorphism (rs6887695) in the disease susceptibility and clinical phenotypes of psoriasis vulgaris patients in the Chinese Han population. The genotype data of the IL-12B gene polymorphism (rs6887695) in 575 psoriasis patients and 1,403 normal controls were investigated using TaqMan technology. The Chi-square test was used to compare the genotype and allele frequency distribution among the groups. The genotypic and allelic frequencies of rs6887695 in the IL-12B gene between the cases and controls, as well as between the guttate and plaque psoriasis cases, were statistically significant (P _genotype <0.01, P _allele <0.01). However, the differences between the pediatric and adult onset psoriasis patients, between familial and sporadic cases, and between female and male cases were not statistically significant (P > 0.05). The genetic polymorphism of the IL-12B gene (rs6887695) may be associated with the psoriasis susceptibility in the Chinese Han population, especially for the plaque cases, but not associated with the age at onset, family history, or sex.     

蒙古族寻常性银屑病与HLA-Cw及DRB1位点相关性研究

【摘要】 目的 探讨蒙古族人群寻常性银屑病与HLA-Cw 及DRB1等位基因的相关性,为银屑病病因学研究提供依据。方法 序列特异性引物聚合酶链反应（PCR-SSP）对蒙古族寻常性银屑病患者81例及正常蒙古族100例进行HLA-Cw及DRB1位点的等位基因进行分型。结果 银屑病组HLA- Cw*06,DRB1*07等位基因频率显著高于健康对照组,HLA- Cw*04、DRB1*04等位基因频率显著低于健康对照组（Pc ＜ 0.05或0.01）。在发病年龄 ＜ 40岁银屑病及家族史阴性患者中HLA- Cw*06、DRB1*07等位基因频率显著高于健康对照组,而HLA- Cw*04、DRB1*04显著低于健康对照组（Pc ＜ 0.05）。在发病年龄≥ 40岁的银屑病及家族史阳性患者中只有HLA- Cw*06等位基因频率显著高于健康对照组（Pc ＜ 0.05）。结论 HLA- Cw*06、DRB1*07等位基因可能是内蒙古地区蒙古族人群寻常性银屑病的易感基因。HLA- Cw*04、DRB1*04等位基因可能是内蒙古地区蒙古族人群寻常性银屑病发病的保护因子。HLA- DRB1*07可能是发病年龄 ＜ 40岁的银屑病的易感基因,而HLA- Cw*04、DRB1*04则可能是发病年龄 ＜ 40岁银屑病的保护因子。     

Association of cytokine gene polymorphisms with psoriasis in cases from the nile delta of egypt

Background:Psoriasis is a chronic inflammatory skin disease with an immunogenetic background. This work was planned to check for the association of polymorphisms related to cytokine genes TNF-α^-308 (G/A), IL-10^-1082 (G/A), IL-6^-174 (G/C), and IL-1Ra (VNTR) with psoriasis in cases from Egypt.Results:Compared to controls, cases showed significant higher frequency of certain genotypes including IL-6^-174 CC (P < 0.001, OR = 6.7), IL-10^-1082 GG (P < 0.05, OR = 5.1), and TNF-α^-308 GG (P < 0.05, OR = 3.7). TNF-α^-308 GG and IL-10^-1082 GG genotypes were higher among cases with plaque subtype of moderate severity. Combined heterozygosity for IL-10 GA, IL-6 GC with TNF GA showed a significant low frequency among studied cases.Conclusion:Genetic polymorphisms related to IL6, IL10, and TNF-α genes showed a particular pattern of association with psoriasis that may have a potential impact on disease counseling and management.