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.     

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.     

内蒙古蒙古族和汉族人群白细胞介素12通路相关基因多态性与寻常型银屑病相关性及与HLA-Cw*0602交互作用研究

【摘要】 目的 探讨白细胞介素12（IL-12）通路相关基因多态性与内蒙古蒙古族和汉族寻常型银屑病患者的遗传相关性及与HLA-Cw*0602的交互作用。方法 收集2012年12月至2018年3月于内蒙古医科大学附属医院住院的寻常型银屑病患者1 409例为病例组,其中汉族1 030例,蒙古族379例,健康对照组1 483例,其中汉族965例,蒙古族518例。采集受试者外周静脉血5 ml提取DNA,选择位于IL-12B（rs2082412、rs2288831、rs3212227、rs3213094、rs7709212）、IL-23R（rs11209026、rs2201841、rs7530511）、IL-28RA（rs4649203）基因区域的9个单核苷酸多态性（SNP）,利用二代测序法进行基因多态性检测,利用序列特异性引物PCR对HLA-Cw*0602进行基因分型。利用PLINK1.07软件进行统计分析,χ2检验比较两组等位基因频率,并计算等位基因的相对危险度估计值比值比（OR）,R × C列联表卡方检验进行单倍型分析。结果 IL-12B基因rs2082412、rs2288831、rs3212227、rs3213094、rs7709212等位基因频率在汉族病例组显著低于汉族对照组（P < 0.005）;IL-12B基因rs3213094等位基因频率在蒙古族病例组显著低于蒙古族对照组（P < 0.005）。汉族和蒙古族病例组HLA-Cw*0602阳性率均显著高于相应民族对照组（P < 0.005）。分层分析显示,汉族HLA-Cw*0602阳性病例组IL-12B基因rs2082412、rs2288831、rs3212227、rs3213094、rs7709212等位基因频率显著低于汉族对照组（P < 0.005）,而阴性病例组与汉族对照组各等位基因频率差异无统计学意义（P > 0.05）。蒙古族HLA-Cw*0602阳性或阴性病例组各等位基因频率与相应对照组差异均无统计学意义（P > 0.005）。分析IL-12B基因区域的5个SNP构建单倍型,在汉族、蒙古族病例组和对照组中6个单倍型分析差异均无统计学意义（P > 0.005）。基于HLA-Cw*0602分层的IL-12B基因多态性单倍型分析,蒙古族、汉族7个单倍型无论HLA-Cw*0602阳性和阴性病例组及对照组中的频率差异无统计学意义（P > 0.005）。HLA-Cw*0602阳性和阴性蒙古族病例组和对照组,单倍型GATGT频率在两组间差异均无统计学意义（P > 0.05）。结论 IL-12通路相关基因多态性与内蒙古蒙古族、汉族人群寻常型银屑病具有相关性,且IL-12B与HLA-Cw*0602在寻常型银屑病发病过程中可能存在交互作用。     

A study of PSORS1C1 gene polymorphisms in Chinese patients with psoriasis

BACKGROUND: Although genetic analyses have identified the HLA-Cw*0602 allele as the major risk allele for chronic plaque psoriasis in various ethnic groups, it has been proposed that the association of Cw*0602 is due to linkage disequilibrium and that other nearby genes are involved in susceptibility to psoriasis. The psoriasis susceptibility 1 candidate 1 (PSORS1C1, formerly SEEK1) gene, located 127 kb telomeric to the HLA-C locus, is considered to be one of the potential candidate genes of psoriasis. Up to the present, no association study of the PSORS1C1 gene has been conducted on Chinese patients with psoriasis. OBJECTIVES: We aimed to determine whether the genetic polymorphisms of the PSORS1C1 gene were associated with an increased risk of psoriasis in Chinese patients. METHODS: We investigated the PSORS1C1 gene for disease association by direct sequencing of the PSORS1C1 gene in 143 Chinese patients with chronic plaque psoriasis and 188 control subjects. Genotyping for HLA-Cw*0602 and the alpha-helix coiled-coil rod homologue (C6orf18, formerly HCR) gene was also carried out using a sequence-based typing method. RESULTS: We identified 10 single nucleotide polymorphisms (SNPs) on the PSORS1C1 gene in our subjects; four of these SNPs cause amino acid change. We also detected poly(C) repeat variants from nucleotide positions 386-392 (poly(C)6-8). The poly(C) repeat polymorphisms cause a frame shift mutation. Another poly(C) repeat variant was also found at nucleotide positions 748-751. No significantly different allelic distributions of the PSORS1C1 SNPs or poly(C) repeat polymorphisms could be found between the patients with chronic plaque psoriasis and controls after correction for multiple testing. However, a significant increase of the Cw*0602 allele and tryptophan-tryptophan allele of the C6orf18 gene (HCR*WW) was found in patients with early onset psoriasis (21.9% vs. 4.8%, P < 10(-7)). Haplotype-based association analysis also showed a susceptibility haplotype carrying Cw*0602 and HCR*WW alleles in early onset Chinese patients. CONCLUSIONS: Our results indicate that the PSORS1C1 gene might not play an important role in the causation of chronic plaque psoriasis in Chinese people.     

包头地区寻常性银屑病与HLA-Cw* 0602等位基因的相关性研究

目的探讨包头地区汉族寻常性银屑病患者与HLACw0602等位基因的相关性。方法采用聚合酶链反应序列特异引物(PCRSSP)法,检测52例寻常性银屑病患者及60名健康对照者的等位基因频率,并相互比较。结果①HLACw0602与包头地区汉族寻常性银屑病患者具有明显的相关性(OR=3.47,P<0.01);②HLACw0602在Ⅰ型、Ⅱ型寻常性银屑病患者中分布无差异(χ2=0.006,P>0.05)。结论HLACw0602可能是寻常性银屑病易感基因或与易感基因相连锁。     

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.     

内蒙古蒙古族寻常性银屑病与HLA-Cw*0602,-DQB1等位基因的相关性

目的探讨内蒙古蒙古族寻常性银屑病与HLA-Cw*0602,-DQB1等位基因的关联性。方法利用序列特异性引物-聚合酶链反应(PCR-SSP)分型技术,对蒙古族寻常性银屑病患者65例及对照组正常蒙古族60例样本进行分型检测并比较分析。结果①寻常性银屑病患者组HLA-Cw*0602,-DQB1*0201等位基因频率较对照组明显升高,差异有统计学意义(P0.05);②HLA-Cw*0602,-DQB1*0201在Ⅰ型及家族史阳性银屑病患者中显著升高(P0.05);③HLA-DQB1*0301在患者组中有显著下降(P0.05)。结论①HLA-Cw*0602及-DQB1*0201可能是内蒙古地区蒙古族寻常性银屑病的易感基因;有家族史和无家族史银屑病患者可能存在遗传背景上的差异。     

Comparison of clinical features of HLA-Cw*0602-positive and -negative psoriasis patients in a Han Chinese population

HLA-Cw6 is strongly associated with psoriasis and has been suggested to be the PSORS1 gene that confers susceptibility to early-onset psoriasis. In this study of the clinical features of HLA-Cw*0602-positive and -negative psoriasis patients in a Han Chinese population, we typed HLA-C in a cohort of 679 patients and compared the two groups. Cw*0602-positive patients (n=345) had an earlier disease onset (p < 1 x 10(-5)), more severe disease (p < 1 x 10(-3)), higher frequency of guttate psoriasis (p < 1 x 10(-9)), more affected legs and trunk (p < 1 x 10(-5)), higher incidence of K?bner's phenomenon (p=0.005) and of trauma history (p=0.009). Cw*0602-negative patients (n= 334) had more palmoplantar pustulosis (p=0.004), nail changes (p=0.001) and scalp involvement (p=0.007). However, there was no statistically significant difference between the two groups regarding age, gender, incidence of plaque psoriasis, erythrodermic, inverse, psoriatic arthritis, and the precipitation factors stress and infection. The study showed that Cw*0602-positive patients had some obvious clinical differences from Cw*0602-negative patients in a Han Chinese population, which provides evidence for an HLA-Cw*0602-associated phenotype in psoriasis.     

Distinct HLA-C/KIR genotype profile associates with guttate psoriasis

Psoriasis is a multifactorial disease with a strong genetic background. It associates strongly to HLA-Cw*0602. HLA-C interacts with killer immunoglobulin-like receptors (KIR) on natural killer (NK) and some natural killer-T (NKT) cells. KIR's function is triggered by specific binding to HLA ligands, which depends on the amino acid 80 of the MHC class I alpha-chain. This permits classifying all HLA-C alleles into two functional groups: asparagine (N80) or lysine (K80) carrying alleles. Psoriasis patients recruited at disease onset were categorized as guttate, vulgaris without arthropathy and vulgaris with arthropathy plus skin lesions. Patients and carefully matched controls were genotyped for position 80 of HLA-C and for KIR. Based on possible HLA/KIR combinations, individuals were classified according to expected NK/NKT cell responses: balanced (B), excess inhibition (EI), excess activation (EA), or undetermined (U). HLA-Cw6 and position 80 genotyping associated strongly to disease, whereas KIR2DS1 associated weakly. Individuals of the U and EI classes were more common among guttate psoriasis patients, which related to HLA-Cw*0602 status. These results suggest that different levels for NK/NKT cell activation thresholds, not only reduction, contribute to immune deregulation in psoriasis. In the guttate phenotype, balanced HLA-C/KIR interactions might be altered by the presence of concomitant streptococcal infections.     

Association of HLA class I alleles with psoriasis vulgaris in southeastern Chinese Hans

BACKGROUND: Predisposing genetic factors in psoriasis include associations with human leukocyte antigen (HLA). Accumulative evidence has shown that certain HLA at class I locus, especially HLA-Cw6, are associated closely with psoriasis. OBJECTIVE: To evaluate the association of HLA class I alleles with susceptibility to psoriasis in the southeastern Chinese Han population. METHODS: We performed genotype for HLA-A, -B and -C loci in 166 patients with psoriasis vulgaris by means of polymerase chain reaction with sequence-specific primers technique. The distribution of HLA allelic frequencies was further analyzed according to age of onset, i.e. under 35-y and beyond 35-y groups. These data were compared with the healthy controls of 204 unrelated Hans. RESULTS: The frequencies of HLA-A*26 (24.7% vs. 13.1%, OR=2.36, Pc<0.01), -B*13 (27.2% vs. 14.8%, OR=2.34, Pc<0.01), -B*27 (12.2% vs. 4.0%, OR=3.49, Pc<0.01) and -Cw*0602 (17.9% vs. 5.3%, OR=4.20, Pc<0.001) were significantly increased in psoriasis patients, whereas HLA-Cw*0304 frequency (4.9% vs. 13.4%, OR=0.32, Pc<0.01) was highly decreased, when compared to the controls. HLA-A*26-B*27-Cw*0602 was identified as a high-risk haplotype of HLA class I in developing psoriasis in the test. HLA-Cw*0602 was found to be strongly associated with the early-onset psoriasis (age of onset <35 y). CONCLUSION: This study demonstrated the positive associations of HLA class I markers with psoriasis vulgaris, of which HLA-Cw*0602 was the strongest susceptibility determinant for development of early-onset psoriasis, in the southeastern Chinese Han population.     

Psoriasis patients who are homozygous for the HLA-Cw*0602 allele have a 2.5-fold increased risk of developing psoriasis compared with Cw6 heterozygotes

BACKGROUND: Psoriasis is strongly associated with certain human leucocyte-associated antigens, especially HLA-Cw*0602. Patients who are HLA-Cw*0602 positive have been reported to have more active disease and a younger age at disease onset than HLA-Cw6-negative patients. OBJECTIVES: To ascertain whether there are differences in the clinical features and relative risk between HLA-Cw*0602 homozygous and heterozygous psoriasis patients. METHODS: One thousand and six patients with chronic plaque psoriasis were evaluated clinically and HLA-C typed. In addition, 512 unrelated controls were typed for HLA-C. RESULTS: Of the patients 646 (64.2%) were HLA-Cw*0602 positive, and 68 (6.8%) were homozygous for this allele. Heterozygosity was associated with a relative risk of developing psoriasis of 8.9 compared with 23.1 for the Cw6 homozygous patients. The homozygous patients also had an earlier disease onset (mean 15.0 vs. 17.8 years, P = 0.04). However, the Cw6 homozygotes did not differ from the heterozygotes with respect to disease severity, guttate onset, distribution of plaques, nail changes or any other clinical parameter recorded. CONCLUSIONS: Homozygosity for the gene in the major histocompatibility complex region has a major additive impact on the risk of developing psoriasis and predisposes to an earlier disease onset, but does not have any marked influence on the phenotype or the severity of the disease.     

Associations of IL-2 and IL-4 gene polymorphisms with psoriasis in the Korean population

BACKGROUND: Psoriasis is association with an overexpression of T-helper cell type 1(Th1) cytokines and relative underexpression of Th2 cytokines. The cytokine production is under genetic control, and certain allelic variants of cytokine genes are associated with higher or lower cytokine production in vitro and in vivo. OBJECTIVES: We aimed to evaluate association of cytokine genes polymorphisms with psoriasis in the Korean population. METHODS: We investigated the polymorphisms of IL-2 -330, IL-4 -590, IL-4 receptor +1902, IL-10 -1082 and -819, and IFN-gamma intron 1 in 114 psoriasis patients and 281 healthy normal controls in Korean. RESULTS: IL-2 -330*G and IL-4 -590*C alleles significantly increased in psoriasis patients, especially late-onset group, compared to the control. The combined effect of IL-2 -330*G and IL-4 -590*C showed that the positive combination of IL-2 -330*G and IL-4 -590*C alleles were more significantly associated with the late-onset group of psoriasis patients than the controls. CONCLUSIONS: These results suggest that the genetic polymorphisms of IL-2 and IL-4 genes can be susceptible to psoriasis in Korean, especially late-onset psoriasis group.     

Distinct clinical differences between HLA-Cw*0602 positive and negative psoriasis patients--an analysis of 1019 HLA-C- and HLA-B-typed patients

A major susceptibility gene for psoriasis is located in the major histocompatibility complex class I region on chromosome 6 very close to the HLA-Cw6 gene. We collected a cohort of 1,019 patients with chronic plaque psoriasis. The patients were typed for HLA-C and HLA-B. A total of 654 (64.2%) were HLA-Cw*0602 positive but 365 (35.8%) carried other HLA-C alleles. We confirmed that HLA-Cw*0602 positive patients have younger age of onset (17.5 vs 24.3 years, P<10(-10)), higher incidence of guttate and the eruptive type of psoriasis (P<0.0001), more frequent exacerbations with throat infections (P=0.01), higher incidence of the Koebner's phenomenon (P=0.01), and more extensive disease (P=0.03). A striking new finding was a diverging pattern of disease severity in HLA-Cw*0602 positive and negative patients depending on the age of onset of the disease (P=0.0006). HLA-Cw*0602 positive women also had more frequent remissions during pregnancy (P<0.0001). All types of nail changes were, however, more common in the Cw*0602 negative patients (P=0.003) and they more often had multiple types of nail lesions (P<0.0001). The three ancestral haplotypes of Cw*0602 all conferred an increase in odds ratio but showed no difference in any of the clinical features studied. Our findings indicate that the genetic factor on chromosome 6 has a strong influence on the phenotype of the disease, and underline that differences in clinical features of psoriasis may be to a large extent genetically determined.     

寻常性与关节病性银屑病发病机制的差异

关节病性银屑病和寻常性银屑病为银屑病的两个临床亚型,其临床表现上的差异可能与遗传、免疫及环境因素等相关.HLA-B、MICA＊00801纯合子、CARD15、TNF＊-857T、TRAF3IP2及IL-13等基因在关节病性银屑病患者中的频率较高;HLA-Cw＊06、MICA＊016、LCE等基因在寻常性银屑病患者中的频率较高.CD8＋T细胞、TNF-α及IL-22在关节病性银屑病的关节损伤中起重要作用;CD4＋T细胞、血管生长因子等与皮肤损害相关.感染、损伤、体力劳动等因素与关节病性银屑病患者发病相关性较高;吸烟、饮酒与关节病性银屑病的发病似乎呈负相关.     

HLA—Cw＊0602与银屑病的关联研究

为研究HLACw*0602与DRB1*07两个基因在银屑病发病中的作用,采用PCRSSP基因分型方法,用一对引物扩增DRB1*073对引物扩增Cw*0602,扩增引物在含溴乙锭的1%琼脂糖凝胶电泳后,紫外灯下定型。结果,病人组和对照组Cw*0602阳性数分别为63.0%和7.4%,RR=21.3P<0.00001DRB1*07为54.3%和18.5%,RR=5.2P<0.0003。表明HLACw*0602是与银屑病关联的基因之一。     

SPR1 gene near HLA-C is unlikely to be a psoriasis susceptibility gene

Although genetics analyses have identified the HLA-Cw6 allele to be the major risk allele for psoriasis vulgaris (PV) in many racial groups, it has been proposed that other putative genes near the HLA-C locus are involved in PV susceptibility and that the association of Cw6 is a result of linkage disequilibrium. The SPR1 gene, a predicted gene located 128 kb telomeric to the HLA-C locus, is considered to be one potential candidate gene of PV. Until now, no association study of the SPR1 gene has been conducted on psoriasis patients. We investigated the SPR1 gene for disease association by direct sequencing of the SPR1 gene in 116 Chinese patients with PV and 116 normal subjects. Genotyping for HLA-Cw6 was also carried out using polymerase chain reaction/restriction fragment length polymorphism. Significant increase of the HLA-Cw6 allele was found in psoriasis patients (32.8% vs. 13.8%, P = 0.001). We found that the SPR1 gene is a highly polymorphic gene containing 13 single nucleotide polymorphisms (SNPs), two of which have not been previously reported, and four SNPs cause amino acid change. No significantly different allelic distribution of 13 SPR1 SNPs could be found between the patients with PV and controls after correction for multiple testing. If the frequencies of SPR1 SNPs were compared between the early onset psoriatics and control subjects, early onset patients were more likely to have G allele at position 988 (60% vs. 35.3%, P = 0.001). However, the significance disappeared upon stratification for the Cw6 status. Haplotype-based association analysis showed two susceptibility haplotypes (types 8 and 19) in early onset psoriasis patients. Nonetheless, the significance also disappeared after stratification of the Cw6 status. Our results suggest that HLA-Cw6 remains the major risk allele in Chinese psoriatics, and that the SPR1 gene might not play an important role in the causation of PV.     

Association of TAP and HLA-DM genes with psoriasis in Koreans

To investigate the possible involvement of antigen-processing genes in the pathogenesis of psoriasis, we analyzed the polymorphisms of the TAP1, TAP2, LMP2, LMP7, DMA, and DMB genes in 98 Korean psoriasis patients and compared them with 184 healthy controls. The frequencies of TAP2*B/B [relative risk (RR)=3.6, p<0.0002] and TAP2*B (RR=1.7, p<0.05) were significantly increased, but TAP1*B (RR=0.3, p<0.002) and TAP2*A (RR=0.6, p<0.03) were significantly decreased, in the patients compared to the controls. We performed further analysis on the TAP1 and TAP2 single nucleotide polymorphisms and found significant differences between the patients and controls in TAP1 single nucleotide polymorphism at position 637 and in TAP2 at 665. In HLA-DM, DMA*0102 (RR=2.5, p<0.0003) was significantly increased, but DMA*0101/0101 (RR=0.4, p<0.0004) and DMB*0103/0103 (RR= 0.3, p<0.005) were significantly decreased in the patients compared to the controls. The TAP and HLA-DM alleles were also analyzed according to the age of onset of psoriasis in the patients (types I and II). It was found that the HLA-DM alleles showed a greater association in type I than type II patients. An analysis of the linkage disequilibrium and stratification also indicated that the alleles of TAP and HLA-DM might be independently associated with HLA-Cw*0602 in psoriasis patients. The stratification analysis between DMA*0101/0101 and DMB*0103/0103 showed that a certain factor, controlled by a gene located between DMA and DMB, might provide strong protection against psoriasis, independently of Cw*0602, in our Korean population. In conclusion, our data suggest that the TAP and HLA-DM alleles could lead to genetic susceptibility toward psoriasis in Koreans.