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Most psoriasis-related genes or loci identified by GWAS represent common clusters and are located in noncoding regions of the human genome, providing only limited evidence for the roles of rare coding variants in psoriasis. Two exome-wide case-control genotyping data sets (11,245 cases and 11,177 controls) were obtained from our previous study. Quality controls were established for each data set, and the markers remaining in each set were annotated using ANNOVAR. Gene-based analysis was performed on the annotation results. A total of 250 and 35 genes in the Exome&#95;Fine and Exome&#95;Asian array cohorts, respectively, exceeded the threshold (P < 4.43 × 10 -6 ). Merged gene-based analysis was then conducted on the same set of SNPs from seven genes common to both arrays, and the chi-square test was used to confirm all gene-based results. Ultimately, four susceptibility genes were identified: BBS7 (P combine  = 1.38 × 10 -29 ), GSTCD (P combine  = 8.35 × 10 -47 ), LIPK (P combine  = 1.02 × 10 -19 ), and PPP4R3B (P combine  = 1.79 × 10 -33 ). This study identified four susceptibility genes for psoriasis via a gene-based method using rare variants, contributing to our understanding of the pathogenesis of psoriasis., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Genome-wide association studies have recently identified a number of non-major histocompatibility complex regions associated with psoriatic arthritis. However, data on Chinese patients with psoriatic arthritis and the differences between psoriatic arthritis and cutaneous psoriasis are limited. This study genotyped 12 single nucleotide polymorphisms in 379 patients with psoriatic arthritis, 376 with cutaneous psoriasis, and 760 healthy controls using Sequenom's Mass ARRAY system. The aim of the study was to expand the database for psoriatic arthritis and cutaneous psoriasis, and develop a genetic prediction system for the early diagnosis of psoriatic arthritis in the Chinese population. One variant in NFKBIA, rs12883343, had a significantly different association with psoriatic arthritis than with cutaneous psoriasis (p = 4.93×10-10, odds ratio 2.371). This suggests that there are differences in the pathogenesis of psoriatic arthritis and cutaneous psoriasis.

Background: Recent studies have revealed that DNA methylation (DNAm) could modulate gene expression in psoriasis (Ps). However, the relationship between whole-genome DNAm and gene expression in Ps has not been studied yet., Objectives: To better characterize the relationship between DNAm and gene expression, and to identify biological pathways triggered by changes in methylation involved in the pathogenesis of Ps., Methods: Differentially methylated sites (DMSs) and differentially expressed genes (DEGs) were analysed by comparing 20 involved psoriatic (PP) skin, 20 uninvolved psoriatic (PN) skin and 20 normal (NN) skin biopsies. DEGs in negative correlation with the methylation were entered into further Gene Ontology (GO) and pathway analysis by clusterProfiler package in R program., Results: A total of 290 genes with reverse correlation overlapped in PP vs PN and PP vs NN comparisons. GO categories of reversely-associated genes mainly enriched in T cell activation, type I interferon signaling pathway and defense response to other organism. Pathway analysis revealed superior NOD-like receptor signaling pathway and Measles enriched in the differentially up-regulated transcripts and regulation of lipolysis in adipocytes in the down-regulated transcripts., Conclusions: Our results provided a comprehensive correlation analysis of transcriptome and methylome in Ps. Increased innate immunity and decreased lipid biosynthesis play important roles in the development of psoriatic skin. This integrated analysis shed light on novel insights into the pathogenic mechanisms involved in Ps., (Copyright © 2018 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.)

The aim of this study was to detect IL36RN variant types and frequency in Han patients with generalized pustular psoriasis (GPP) in Sichuan region of China, reveal the difference of variant frequency between GPP alone and GPP + PV (psoriasis vulgaris), and preliminarily clarify the pathogenesis of GPP in this region.Genomic DNA was extracted and subjected to polymerase chain reaction (PCR) for the amplification of the entire encoding and splice sites of the IL36RN gene followed by bidirectional sequencing. Differences in frequencies of IL36RN variants between groups were analyzed by SPSS Statistics 17.0 software. Meanwhile, the IL36RN variant frequency between GPP alone and GPP + PV was compared.The total IL36RN variant frequency was 60.47% in Han GPP patients from Sichuan region of China. Three variant types (c.115 + 6T > C, c.140A > G, c.227C > T) were identified, among which c.115 + 6T > C exhibited the highest frequency (55.81%). All the 3 variants' frequency of GPP alone group had statistical significance when compared with PV patients and normal controls (P < .05). The IL36RN variant frequency of GPP alone group was statistically higher than that of GPP + PV group (79.17% vs 36.84%, P < .05).IL36RN may be the major disease-causing gene in GPP patients in Han population in Sichuan region of China. c.115 + 6T > C is a possible hot-spot mutation within the IL36RN gene. In contrast to GPP + PV, IL36RN mutations possibly play a more important role in the development of GPP alone.

Aim: VEGF and EGF are assumed to be involved in the pathogenesis of psoriasis, while the impacts of their polymorphisms on psoriasis are inconsistent. Therefore, we hope to clarify these relationships in the Chinese Han population., Methods: A total of 131 patients with psoriasis vulgaris and 176 controls were enrolled. The polymorphisms rs833061 (T > C), rs10434 (G > A) in VEGFA, and rs4444903 (G > A), rs2237051 (A > G) in EGF of each participant were detected. The patients were treated with calcipotriol plus acitretin 30 mg/day for 8 weeks., Results: No SNPs of rs833061, rs10434, rs4444903 and rs2237051 were found to be associated with psoriasis susceptibility and efficacy. Although the mutation of rs10434A was associated with baseline disease severity (p = 0.026), and rs2237051G allele was associated with increased erythema during treatment (p = 0.015)., Conclusion: The allele of rs2237051 G increased the erythema during the treatment, and no polymorphism of VEGF and EGF gene was found to be associated with the susceptibility and efficacy in psoriasis.

Purpose: To investigate the clinical features of 51 uveitis patients with psoriasis in China., Methods: The psoriasis type, demographics, ocular findings, auxiliary examination findings, complications, and therapeutic effects were analyzed., Results: A total of 37 male and 14 female uveitis patients with psoriasis were classified into four groups: psoriasis vulgaris (29 cases); psoriatic arthritis (15 cases); psoriatic erythroderma (6 cases); and pustular psoriasis (1 case). The onset age of psoriasis was younger than for uveitis (p < 0.001). Anterior uveitis, panuveitis, and posterior uveitis was observed in 58.8%, 35.3%, and 5.9% of the patients, respectively. Hypopyon was more frequently noted in the group with psoriatic arthritis (p = 0.007). Optic disc staining was more frequently noted in the group with psoriatic erythroderma (p = 0.029). Significant visual improvement was observed in 17 patients., Conclusions: Uveitis can be associated with various types of psoriasis in China, but was most frequently observed in patients with psoriasis vulgaris and psoriatic arthritis.

Background: Psoriasis is a chronic inflammatory skin disease characterized by epidermal hyperproliferation and altered keratinocyte differentiation and inflammation and is caused by the interplay of genetic and environmental factors. Previous studies have revealed that DNA methylation (DNAm) and genetic makers are closely associated with psoriasis, and strong evidences have shown that DNAm can be controlled by genetic factors, which attracted us to evaluate the relationship among DNAm, genetic makers, and disease status., Methods: We utilized the genome-wide methylation data of psoriatic skin (PP, N  = 114) and unaffected control skin (NN, N  = 62) tissue samples in our previous study, and we performed whole-genome genotyping with peripheral blood of the same samples to evaluate the underlying genetic effect on skin DNA methylation. Causal inference test (CIT) was used to assess whether DNAm regulate genetic variation and gain a better understanding of the epigenetic basis of psoriasis susceptibility., Results: We identified 129 SNP-CpG pairs achieving the significant association threshold, which constituted 28 unique methylation quantitative trait loci (MethQTL) and 34 unique CpGs. There are 18 SNPs were associated with psoriasis at a Bonferoni-corrected P  < 0.05, and these 18 SNPs formed 93 SNP-CpG pairs with 17 unique CpG sites. We found that 11 of 93 SNP-CpG pairs, composed of 5 unique SNPs and 3 CpG sites, presented a methylation-mediated relationship between SNPs and psoriasis. The 3 CpG sites were located on the body of C1orf106 , the TSS1500 promoter region of DMBX1 and the body of SIK3 ., Conclusions: This study revealed that DNAm of some genes can be controlled by genetic factors and also mediate risk variation for psoriasis in Chinese Han population and provided novel molecular insights into the pathogenesis of psoriasis.

Background: Calcipotriol/betamethasone dipropionate combination in a non-alcoholic, lipophilic gel formulation (two-compound gel) has previously been demonstrated as a safe and effective treatment for scalp psoriasis in Caucasian, Hispanic/Latino, and Black/African American populations. The purpose of this randomized, investigator-blinded, active-controlled, 4-week study was to evaluate the efficacy and safety of the two-compound gel in Chinese subjects with scalp psoriasis., Method: Subjects were randomized in a 1 : 1 ratio to four weeks of treatment with either the two-compound gel once daily or calcipotriol scalp solution twice daily. Subjects were evaluated after one, two, and four weeks of treatment. The primary efficacy endpoint was the proportion of subjects who achieved "controlled disease" defined as "clear" or "minimal" disease according to investigator's global assessment of disease severity at week 4., Results: The proportion of subjects who achieved "controlled disease" at week 4 was statistically significantly higher in the two-compound gel group (87.5%) than in the calcipotriol solution group (50.8%), (P < 0.0001). Greater and more rapid improvements with the two-compound gel were also observed in clinical signs (redness, thickness, and scaliness) and itching. The two-compound gel was associated with fewer adverse drug reactions than calcipotriol scalp solution (18.6% vs. 33.1%) (P = 0.011)., Conclusions: The calcipotriol/betamethasone dipropionate gel applied once daily was significantly more effective and better tolerated than calcipotriol scalp solution applied twice daily in the treatment of scalp psoriasis over four weeks in Chinese subjects., (© 2015 The International Society of Dermatology.)

Several previous studies including one of them co-authored by our group have revealed that serum and psoriatic plaque expression of matrix metalloproteinase-9 (MMP-9) was significantly upregulated in psoriasis. The aim of this study was to investigate the association of three single nucleotide polymorphisms (SNPs) and haplotypes of MMP-9 (rs3918242, rs3918254 and rs4810482) with psoriasis vulgaris in a Chinese Han population. The serum levels of MMP-9 in 245 psoriasis vulgaris cases and 256 healthy controls were assessed using ELSA kits, and the three SNPs were genotyped using polymerase chain reaction-ligation detection reaction (PCR-LDR) method. Four haplotypes based on the three SNPs were also analyzed. Our study showed that the serum MMP-9 levels in patients with psoriasis vulgaris were significantly higher than that in controls (P<0.05). However, the three SNPs were not significantly associated with psoriasis vulgaris susceptibility (all P>0.05). Similar results were found in further subgroup analysis based on gender, age of onset, family history, and serum MMP-9 levels, except that a protective effect of psoriasis vulgaris was detected among female subjects with the CT genotype of rs3918254 (OR=0.47, 95% CI=0.23-0.96, P=0.038), but this association did not survive after Bonferroni correction (P(adj)=0.076). The haplotype analysis also failed to show any association with psoriasis vulgaris. We found no evidence for the association between the MMP-9 polymorphisms and psoriasis vulgaris susceptibility in a Chinese Han population., (Copyright © 2015 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.)

Psoriasis is a chronic inflammatory skin disease that has been associated with abnormal lipid metabolism. To characterize the lipid profile in Chinese, 86 patients with psoriasis and 84 healthy control subjects were assessed. Compared with healthy controls, the fasting serum values of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (ApoA-I) were lower in the patient group. Compared with vulgaris psoriasis, special types of psoriasis had even lower levels of HDL-C and ApoA-I. Considering the severity of psoriasis, the level of ApoA-I and HDL-C were also the only two serum lipid parameters decreased in the mild group compared to those in controls. In the moderate and the severe group, the values of TC, LDL-C, HDL-C and ApoA-I were all decreased compared to healthy control group. Further analysis indicated that the values of HDL-C and ApoA-I were significantly lower in the severe group compared to the moderate group. Correlation analysis indicated that the levels of HDL-C but not ApoA-I was negatively associated with the severity of the disease. Interestingly, when psoriasis was improved by treatment, the serum levels of TG, TC, HDL-C and ApoA-I were increased from the pre-treatment values. We conclude that abnormalities in serum lipid metabolism may play an important role in the pathogenesis of Chinese patients with psoriasis.

Background: Ustekinumab, an interleukin-12/23 inhibitor, is effective in the treatment of psoriasis. A recent Italian study showed more favourable response to ustekinumab in patients with positive human leucocyte antigen (HLA)-Cw6. Nonetheless, there are differences in genetic susceptibility to psoriasis between races, and no studies have specifically assessed the candidate genetic markers in predicting therapy outcome in Chinese patients with psoriasis treated with ustekinumab., Objectives: To determine whether HLA gene polymorphisms can predict the response to ustekinumab in Chinese patients with psoriasis., Methods: Sixty-six patients with psoriasis treated with ustekinumab were included in the study, and the effectiveness of ustekinumab therapy was evaluated at weeks 0, 16 and 28 by Psoriasis Area and Severity Index (PASI)., Results: More HLA-Cw6-positive patients achieved a PASI 75 response at week 4 compared with HLA-Cw6-negative patients (38% vs. 9%, P = 0·019). Similarly, at week 16, patients carrying the HLA-Cw6 allele showed a higher likelihood of achieving PASI 50, 75 and 90 than Cw6-negative patients, although this was not statistically significant. At week 28, a significantly higher percentage of HLA-Cw6-positive patients maintained PASI 90 response compared with Cw6-negative patients (63% vs. 26%, P = 0·035). Further analysis of other HLA allele polymorphisms did not show significant associations with therapeutic response to ustekinumab., Conclusions: This pharmacogenetic study provides preliminary data indicating that positive HLA-Cw6 is associated with a good response to ustekinumab treatment in Chinese patients with psoriasis., (© 2014 British Association of Dermatologists.)

Background: Copy number variations of FCGR3B are associated with several immune related diseases such as systemic lupus erythematosus, rheumatoid arthritis and primary Sjögren's syndrome. Little is known about the association between FCGR3B copy number variants and psoriasis., Objective: To investigate whether FCGR3B copy number variants are associated with susceptibility to psoriasis vulgaris in the Chinese Han population., Methods: 343 psoriasis vulgaris patients and 574 healthy individuals were recruited as cases and controls. TaqMan® Copy Number Assays were performed to quantify the copy numbers in the FCGR3B locus. CopyCaller v1.0 software and R (version 2.15.3) were used to do the subsequent statistical analysis., Results: A significant association between psoriasis vulgaris and a high copy number (>2) of FCGR3B was observed (odds ratio = 1.63, 95% confidence interval 1.09-2.45, p < 0.02). However, the low copy number of FCGR3B was not significantly associated with psoriasis vulgaris., Conclusion: A high copy number of FCGR3B is associated with psoriasis vulgaris in Han Chinese.

Background: The vitamin D receptor (VDR) is a master regulator of epidermal barrier function, inflammation, stem-cell proliferation, and microbial defense., Objective: To evaluate the association between the VDR and psoriasis in the northeastern Chinese Han population., Methods: In 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., Results: The 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)., Conclusions: These data suggest that VDR polymorphisms are associated with psoriasis in Northeastern Han Chinese population., (Crown Copyright © 2013. Published by Elsevier Ireland Ltd. All rights reserved.)

Background: Recent work using genome–wide association studies (GWAS) in Chinese Han and white populations have discovered several novel psoriasis susceptibility genes., Aim: To examine whether the risk loci for psoriasis identified in previous GWAS in a white population are also associated with psoriasis in a Chinese Uygur population in Xinjiang., Methods: Genotyping analysis of eight single-nucleotide polymorphisms (SNPs) associated with psoriasis was performed for 539 patients with psoriasis and 749 controls, all of Chinese Uygur descent, using a commercial assay., Results: Two SNPs had an association with psoriasis in this Chinese Uygur population: SNP rs495337 in the gene encoding for zinc finger protein 313 (P < 0.001; OR = 0.80) and SNP rs20541 of the gene encoding for interleukin-13 (P < 0.001; OR = 0.82). In subgroup analyses, the two SNPs were significantly associated (P < 0.05) with type I psoriasis, Rs495337 showed statistically difference between positive family history of psoriasis patients and controls whereas rs20541 might preferentially associated with negative family history psoriasis patients. Interestingly, using multifactor dimensionality reduction, a significant two-locus interaction was seen between rs495337 and rs20541, with a crossvalidation consistency of 4/5 and average balanced prediction (accuracy 55.5%, P < 0.001)., Conclusions: ZNF313 and IL-13 are associated with risk for psoriasis in a Chinese Uygur population, and there is an effect of interaction between the two genes on this risk.

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.

Investigations about prevalence of obesity in psoriasis patients are increased nowadays. Higher serum levels of leptin in patients with psoriasis who are overweight or obese suggest that leptin may serve as a molecular link between psoriasis and metabolic comorbidities. However, the pathological functions of leptin in psoriasis are not clearly understood. We investigated the influence of being overweight or obese on the risk of psoriasis, and the relationship between serum leptin levels and the severity of psoriasis in Chinese Han patients. We also investigated biological effects of leptin on the proliferation and secretion of pro-inflammatory cytokines by human keratinocytes in vitro. Obesity was a significant risk factor for psoriasis in the Chinese Han population; however, we did not observe a significant correlation between Psoriasis Area and Severity Index (PASI) and body mass index (BMI). We observed a positive correlation between the serum leptin level and PASI in overweight and obese male patients with psoriasis. Strong leptin immunoreactivity was detected in the epidermis of psoriatic lesions, particularly in keratinocytes. Leptin significantly increased the proliferation and secretion of pro-inflammatory cytokines by keratinocytes in vitro. In conclusion, this study suggests leptin as a novel molecular link between psoriasis and obesity, which may help to explain the more server conditions of psoriasis in patients with obesity., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The Dermatology Life Quality Index (DLQI) is one of the most frequently used scales to evaluate the impact of skin disease on patients' quality of life (QoL). There has not been psychometric evaluation of the Chinese version of DLQI in Chinese patients with psoriasis., Objective: The objective of this study was to evaluate the psychometric properties of the Chinese version of DLQI., Methods: Patients with psoriasis (≥ 18 years old) visiting nine hospitals in various regions of China were enrolled in the study. The DLQI, Psoriasis Disability Index (PDI) and Health Survey Short Form (SF-36) were completed. Severity of psoriasis was assessed by the Psoriasis Area Severity Index (PASI). Reliability was estimated by internal consistency. Validity was assessed using known-groups comparison, convergent validity and construct validity., Results: In all, 851 patients were included in the study. The internal consistency reliability of the DLQI was high (Cronbach's alpha = 0.91). Known-groups comparison showed that the DLQI discriminated well among patients who differed in age, geographical region, duration of psoriasis and the PASI score. Evidence of convergent validity of the DLQI was proved by high correlations with the PDI and four subscales of SF-36 (role-physical, bodily pain, social functioning and role-emotional): r = 0.52-0.78. Construct validity was proved by the presence of one-factor structure that accounted for 55.9% of the variance and fitted well into the unidimensional model., Conclusion: The Chinese version of DLQI is a reliable and valid measure to assess patient-reported impact of skin disease and could be used in QoL and health outcome studies on Chinese psoriasis patients., (© 2011 The Authors. Journal of the European Academy of Dermatology and Venereology © 2011 European Academy of Dermatology and Venereology.)

Psoriasis is a chronic inflammatory skin disease with multifactorial etiology. Connexin 26 (Cx26), an important gap junction protein, has been found highly expressed in plaques of psoriasis. Recently, genome wide association studies (GWAS) identified one new single nucleotide polymorphism (SNP) in GJB2 gene coding for Cx26 protein associated with psoriasis in Chinese Han population. In this paper, we verified the GWAS data in Chinese Han population. Here we genotyped the polymorphism of GJB2 rs3751385:C>T in 371 psoriasis patients and 330 healthy controls in Chinese Han population using polymerase chain reaction restriction fragment length polymorphism assay (PCR-RFLP). Our case-control assay indicated decreased frequency of the GJB2 rs3751385 C allele in psoriasis patients compared with that in the healthy controls [p = 6.02 × 10(-5), Odds ratio (OR) = 0.793, 95 % confidence interval (CI) 0.706-0.889]. The result suggested that GJB2 gene polymorphism rs3751385:C>T was associated with psoriasis susceptibility of Chinese Han population.

Loss-of-function mutations in filaggrin gene (FLG; OMIM #135940) have been reported to cause the semi-dominant keratinizing disorders such as ichthyosis vulgaris (IV; OMIM #146700) and atopic dermatitis (AD; OMIM #605803). Recent linkage analysis and immunohistochemical studies suggest the possible contribution of FLG to psoriatic susceptibility. However, no susceptibility variant in FLG gene associated with psoriasis (OMIM #177900) has been identified. In this study, we identified a non-sense mutation of FLG (p.K4022X) in a Chinese psoriasis/IV coexisting family. The homozygous p.K4022X mutation was detected in a psoriasis patient, whereas the heterozygous p.K4022X mutation was identified in two IV patients and four apparently normal family members. We also genotyped p.K4022X variant in 441 sporadic Chinese psoriasis patients and found homozygous mutation in two patients, while no homozygous variant was found in 500 control individuals. After sequencing the entire coding region of FLG gene in 441 psoriasis patients, we identified another five mutations (p.R826X, p.W2583X, c.7945delA, c.3321delA and p.Q2417X). Although all six FLG mutations as a whole was not significantly associated with psoriasis (P = 0.105), mutation p.K4022X was significantly associated with psoriasis (P < 0.05). Our data thus indicates an association of FLG with psoriasis in Chinese population.

Background: HLA-Cw*06 has a strong influence on the clinical features and the susceptibility to psoriasis in different ethnicities. It is also used as a biomarker to predict the therapeutic efficacy of biologics, with inconsistent results. Additionally, most Asian patients with psoriasis do not carry HLA-Cw*06., Objectives: To determine additional HLA alleles which confer susceptibility or affect the severity of psoriasis in Chinese Han individuals. In addition, the potential of using HLA to predict treatment outcomes was also investigated., Methods: We conducted a case-control association study in 199 Chinese patients with psoriasis and 200 unrelated healthy controls. HLA-B and HLA-C genotyping was performed and correlated with the therapeutic efficacy of the biologics, including alefacept, efalizumab, etanercept and ustekinumab. Patients with psoriasis were divided into group A (high-need patients with moderate to severe psoriasis) and B (general patients with psoriasis)., Results: The frequencies of HLA-B*60, HLA-B*75, HLA-Cw*06 and HLA-Cw*10 were significantly increased in patients with psoriasis compared with the healthy controls. However, the prevalence of HLA-Cw*06 was lower in group A compared with group B (6% vs. 17%, Pc=0·04). HLA-B*46 was found to be strongly associated with group A but not with group B patients with psoriasis. HLA-Cw*01/HLA-B*46 was also identified as a risk haplotype for Chinese patients with psoriasis, compatible with the results in Thais. Significant differences in response to biologics were observed between HLA-Cw*01+ and HLA-Cw*01- individuals in the alefacept treatment group, and between HLA-B*37+ and HLA-B*37-, and HLA-B*58+ and HLA-B*58- individuals in the efalizumab treatment group., Conclusions: In addition to HLA-Cw*06, the HLA-Cw*01/HLA-B*46 haplotype was also increased in Chinese patients with psoriasis. High-need patients with psoriasis had a lower frequency of HLA-Cw*06 but a higher prevalence of HLA-B*46 compared with general patients with psoriasis in our population., (© 2011 The Authors. BJD © 2011 British Association of Dermatologists.)

A common deletion comprising LCE3B and LCE3C, members of the late cornified envelope (LCE) gene cluster, has been shown to be significantly associated with psoriasis in several Caucasian populations. The expression of LCE can be induced by skin barrier disruption, leading to psoriatic lesions. To identify whether deletion of genes in the LCE region is a genetic risk factor in the pathogenesis of psoriasis, we genotyped the LCE3C and LCE3B deletion and single-nucleotide polymorphism rs4112788, which is in strong linkage disequilibrium with the LCE gene cluster, via direct sequencing in 468 psoriasis patients and 768 controls in a Chinese population. We found that deletion of the two LCE genes was associated with psoriasis (odds ratio=1.917; 95% confidence interval=1.291-2.847, P=0.001), a conclusion that was similar to that of another independent Chinese cohort study. The deletion was not significantly associated with the age of disease onset, and there was no significant epistatic interaction between deletion and PSORS1 risk allele on 6p21.3. Our study confirms an association between the deletion of LCE3C and LCE3B and psoriasis in a Chinese population.

Psoriasis is an inflammatory skin disease with a multifactorial genetic basis. A recent genome-wide association study identified several psoriasis-predisposing loci, including IL-12B, which encodes the common p40 subunit of interleukin (IL)-12 and IL-23 and the IL-23 receptor gene (IL-23R). To investigate the relationships of these predisposing polymorphisms with psoriasis in the Chinese Han population, we genotyped three representative variants (rs6887695, rs11465817, and rs1343152) in 217 unrelated patients and 288 control subjects using direct sequencing, We further replicated the positive polymorphism, rs6887695, in a larger combined sample that included 578 patients and 1422 controls. We found the single nucleotide polymorphism, rs6887695 (odds ratio = 1.33, 95% confidence interval 1.03-1.73, p = 0.028) of IL-2B to be significantly associated with psoriasis, and a novel halotype A-A of rs11465817-rs1343152 also showed a positive association. Our study confirms the effects of IL-12B and IL-23R variants on psoriasis in East Asian populations, and provides a reference point for further investigation of the role of the IL-12/IL-23 pathway in chronic epithelial inflammation in Asian and other ethnic populations., (Copyright © 2010 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

Background: Psoriasis is a common dermatological disorder, in which autoimmunity plays an important role. CD4(+)CD25(+) regulatory T cells (T-regs) have been suggested to be involved in the pathogenesis of some autoimmune diseases. T-regs express the fork head/winged helix transcription factor, FOXP3, which appears to be of key importance in the development and function of T-regs. Studies have found that single-nucleotide polymorphisms (SNPs) in the FOXP3 gene contribute to susceptibility to some autoimmune disorders. However, information about FOXP3 gene in psoriasis is limited., Objective: This study evaluated the association between FOXP3 gene SNPs and susceptibility to psoriasis in a Han Chinese population., Methods: In a hospital-based case-control study, 524 patients with psoriasis and 549 psoriasis-free controls were recruited according to age and gender. We investigated four SNPs in the FOXP3 gene (-6054, deletion/ATT; -3279, A/C; -924, A/G; IVS9+459, A/G) in psoriatic patients, and assessed allele and genotype frequencies in psoriatic patients (237 females, 287 males) and normal controls (272 females, 277 males). The polymorphisms were genotyped using the PCR sequence-specific primer (PCR-SSP) technique and PCR-restriction fragment length polymorphism (RFLP) analysis., Results: We found that increased risk of psoriasis was associated with the FOXP3 -3279 AC genotype (adjusted OR, 1.32; 95% CI, 1.01-1.74) and the combined AC+AA genotype (adjusted OR, 1.38; 95% CI, 1.07-1.78), compared with the -3279 CC genotype. We also found that an increased risk of psoriasis was associated with the FOXP3 IVS9+459 GG genotype (adjusted OR, 2.24; 95% CI, 1.41-3.58). However, the combined GA+GG genotype showed no such tendency (adjusted OR=1.28; 95% CI, 1.00-1.64), compared with the IVS9+459 AA genotype. There was no evidence of an increased risk associated with the FOXP3-6054 deletion/ATT or FOXP3-924 A/G genotype. In combined genotype analyses, the FOXP3-3279 AC+AA genotype was more obviously associated in males (adjusted OR=1.60, 95% CI=1.11-2.31) and severe psoriasis patients (PASI score >20; adjusted OR=1.97, 95% CI=1.41-2.75). Meanwhile, the FOXP3 IVS9+459 GA+GG genotype was also associated with severe psoriasis patients (adjusted OR=1.69, 95% CI=1.21-2.36)., Conclusions: FOXP3 polymorphisms appear to contribute to the risk of psoriasis in a Han Chinese population. Larger studies are needed to confirm these findings., (Copyright 2009 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.)

Background: Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine that plays an important part in the pathogenesis of autoimmune diseases. A high level of MIF has been detected in plaques of psoriasis and the sera of patients with psoriasis. Polymorphisms associated with autoimmune and inflammatory diseases exist in the promoter region of MIF and alter its expression., Objective: The aim of this study was to evaluate the potential relationship between functional polymorphisms of MIF and psoriasis in a Han population in northeastern China., Methods: Two-hundred-and-forty psoriasis patients and a control group of 269 healthy volunteers were included in this study. We genotyped MIF-173G/C using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). MIF-794CATT(5-8) microsatellite polymorphism was genotyped by polyacrylamide gel electrophoresis (PAGE)., Results: No significant difference in the distributions of alleles, genotypes and haplotypes was observed between patients and controls. When patients were divided into subtypes according to sex, family history and age of onset, distribution of the MIF-173C allele between male and female patients was significantly different (P=0.04). MIF-173C allelic distribution between late onset psoriasis patients and controls was also different (P=0.02), as well as late onset patients and early onset subjects (P=0.04)., Conclusions: These results suggested a preliminary association between the MIF-173C allele and male psoriasis and late onset psoriasis in the studied population. In addition, the distributions of the two polymorphisms in Asian populations were quite different from the other continental populations.

Psoriasis (OMIM#177900) is a common polygenic skin disorder affecting approximately 2% of the northern European population and 0.1% of the Han Chinese. Psoriasis patients suffer from chronic skin inflammation, manifested by erythematous scaly lesions. PSORS1-PSORS9 have been confirmed as psoriasis susceptibility loci in independent genetic studies on predominantly Caucasian populations, with psoriasis susceptibility loci (PSORS1, PSORS9) and additional loci at 9q33-34 and 2p22.3-11.2 reported in Han Chinese patients. In this study, we show the association of PSORS4 with psoriasis in Singaporean Chinese. Dense genotyping of single-nucleotide polymorphism-tagging candidate genes within the epidermal differentiation complex revealed significant association in the proximity of the involucrin gene (IVL); the strongest association was seen in early-onset psoriasis patients (P=0.0014). A follow-up genome-wide association screen localized the psoriasis susceptibility region to approximately 360 kb along chromosome 1 in the vicinity of IVL, small proline-rich region (SPRR) and proline-rich region 9 (PRR9) genes. The study of interactions between the causative variant(s) in this locus will provide insights into a possible role for epidermal barrier formation in the pathogenesis of psoriasis.

Vitiligo is a common skin and hair depigmentary disorder that results from selective destruction of melanocytes. It occurs in a typical multifactorial, polygenic inheritance. Several studies have indicated that vitiligo is associated with some autoimmune diseases. In this paper we examined 6,516 vitiligo patients including clinical characteristics, familial involvement, and their association with other autoimmune diseases. Compared with sporadic vitiligo probands, familial vitiligo probands have earlier age onset and longer disease duration. The prevalences of four autoimmune diseases namely rheumatoid arthritis, chronic urticaria, alopecia areata and psoriasis, were significantly elevated in generalized vitiligo probands and their first-degree relatives. The prevalences of chronic urticaria, rheumatoid arthritis, psoriasis were much higher in familial generalized vitiligo probands. In addition, the prevalences of diabetes mellitus and asthma were also higher in familial vitiligo probands. These findings indicate that generalized vitiligo may share common genetic aetiologic links with other autoimmune diseases, and the genetic component of familial generalized vitiligo is stronger.

Background: Psoriasis is a chronic inflammatory skin disease associated with an HLA-Cw6 allele. Higher waist-hip ratio (WHR) and body mass index (BMI) may increase the risk of psoriasis vulgaris, but, to our knowledge, no evidence of the combined effects of HLA-Cw6 and BMI, WHR are available., Objectives: To evaluate the combined effect of HLA-Cw6, BMI and WHR on psoriasis vaulgaris., Methods: The data of 466 patients and 177 controls were investigated and analyzed by a hospital-based case-control study and non-condition logistic regress model., Results: There was a graded positive association of WHR and BMI with psoriasis vulgaris. Compared with a WHR of 0.80 or less than 0.80, the odds ratio (OR) was 2.36 (p < 0.01) for WHR 0.80-0.85, and 2.74 (p < 0.01) for WHR greater than 0.85. Compared with subjects with a BMI of 20 or less than 20, the multivariate OR of psoriasis were 1.20 (p > 0.05) for a BMI of 20-25, 1.84 (p < 0.05) for a BMI of more than 25 corresponding overweight (p for trend, <0.01). We found not only the risk of psoriasis for the individual with HLA-Cw6+ was 8.33 times greater than that for individual with HLA-Cw6(-) but also the risk increased approximately 35 times in individuals with HLA-Cw6+ and a overweight as compared with one with HLA-Cw6(-) and a non-overweight, and 17-fold when the individuals with HLA-Cw6+ and a WHR of more than 0.80 were compared with individuals with HLA-Cw6(-) and a WHR of 0.80 or less than 0.80, displaying the combined effect of HLA-Cw6, BMI and WHR (all p < 001)., Conclusion: This study suggested that HLA-Cw6, overweight and higher waist-hip ratio are material risk factors of psoriasis vulgaris, specially the combined effects of HLA-Cw6 and BMI, WHR on psoriasis vulgaris in Chinese population.

Objective: Psoriasis and psoriatic arthritis (PsA) are interrelated disorders. To date, no study has compared the differences of genes between patients with PsA and psoriasis and healthy controls in a Chinese population. We conducted a retrospective study to determine the human leukocyte antigen (HLA) -A, -B, -Cw, -DR, and -DQ alleles in Chinese patients with PsA and psoriasis., Methods: HLA studies were performed using polymerase chain reaction sequence-specific oligonucleotide (PCR-SSO) genotyping methods in 91 patients with PsA and 80 with psoriasis and 75 controls. Age at disease onset, sex, disease duration, enthesitis, and uveitis were also analyzed., Results: Among the patients with PsA and psoriasis, the frequency of HLA-B27 was significantly higher in PsA and HLA-A*30, -Cw*06, -DR*07 in psoriasis compared with controls. In contrast, HLA-B*58 was more common in controls than in PsA and psoriasis groups, and the prevalence of HLA-DR*17 was significantly higher in controls than in those with psoriasis. Comparing PsA and psoriasis, the prevalence of HLA-B*27 and HLA-Cw*12 were more common in PsA patients, while the prevalence of HLA-DR*07 was higher in those with psoriasis (p < 0.05). Among PsA patients, the association between HLA-B*27 and axial joint involvement and uveitis was significant (p < 0.05)., Conclusion: Certain HLA alleles are found in Chinese patients with psoriasis (HLA-A*30, -Cw*06, -DR*07) and PsA (HLA-B*27). Psoriasis patients with the HLA-B*27 and/or -Cw*12 may have higher risk of developing PsA. Ours is the first study to assess the genetic role of HLA in patients with psoriasis and PsA in a Chinese population.

Through a series of linkage analyses in a large Chinese family cohort of psoriasis, we previously identified and confirmed a non-HLA psoriasis linkage locus PSORS9 within a small region at 4q31.2-32.1. Within the critical region of the PSORS9 locus, IL-15 has been long recognized as a strong candidate gene for psoriasis. In this study, we investigated the association between IL-15 genetic polymorphisms and psoriasis in a large Chinese sample. Highly significant evidence for association was identified at a single-nucleotide polymorphism (SNP) (g.96516A --> T) within the 3'-untranslated region (UTR) of the IL-15 gene (P=0.00006, after correction for multiple testing). Haplotype analysis using the SNPs within the 3'UTR region also provided strong supporting evidence for association (P=0.00005), where we identified a haplotype of the 3'UTR region of IL-15 associated with increased risk to psoriasis (odds ratio=1.65). This association was also supported by the results of our expression activity analyses, where we demonstrated that the identified risk haplotype is associated with an increased activity of IL-15. Therefore, we provided early evidence for the important role of IL-15 genetic variants in the pathogenesis of psoriasis, probably by increasing interleukin production and inflammation in the lesions of psoriasis.

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.

Power and sample size calculations are critical parts of any research design for genetic association. We present a method that utilizes haplotype frequency information and average marker-marker linkage disequilibrium on SNPs typed in and around all genes on a chromosome. The test statistic used is the classic likelihood ratio test applied to haplotypes in case/control populations. Haplotype frequencies are computed through specification of genetic model parameters. Power is determined by computation of the test's non-centrality parameter. Power per gene is computed as a weighted average of the power assuming each haplotype is associated with the trait. We apply our method to genotype data from dense SNP maps across three entire chromosomes (6, 21, and 22) for three different human populations (African-American, Caucasian, Chinese), three different models of disease (additive, dominant, and multiplicative) and two trait allele frequencies (rare, common). We perform a regression analysis using these factors, average marker-marker disequilibrium, and the haplotype diversity across the gene region to determine which factors most significantly affect average power for a gene in our data. Also, as a 'proof of principle' calculation, we perform power and sample size calculations for all genes within 100 kb of the PSORS1 locus (chromosome 6) for a previously published association study of psoriasis. Results of our regression analysis indicate that four highly significant factors that determine average power to detect association are: disease model, average marker-marker disequilibrium, haplotype diversity, and the trait allele frequency. These findings may have important implications for the design of well-powered candidate gene association studies. Our power and sample size calculations for the PSORS1 gene appear consistent with published findings, namely that there is substantial power (>0.99) for most genes within 100 kb of the PSORS1 locus at the 0.01 significance level., (Copyright 2005 S. Karger AG, Basel.)

Background: Recent studies have demonstrated an association of a polymorphic (GCT)n triplet repeat in the transmembrane (TM) region of the major histocompatibility complex (MHC) class I chain-related gene A (MICA), one of the MHC class I chain-related (MIC) family members, with some autoimmune diseases, including Behçet's disease, acute anterior uveitis, Takayasu's arteritis and others., Objectives: The aim of this study was to examine whether the MICA gene is associated with psoriasis vulgaris (PS) in Chinese., Patients and Methods: The (GCT)n polymorphism of the MICA gene was investigated in 200 healthy Chinese of Han origin and 300 patients with PS by polymerase chain reaction amplification and denaturing polyacrylamide gel electrophoresis., Results: Five alleles, namely A4, A5, A6, A9 and A5.1 were found in both groups. Comparison of the data from both groups revealed that the A5.1 allele was present at a significantly higher frequency in the patient group (41.5%) than in the control group (23.0%) (Pc < 0.0001, Pc means the probability of a comparison with the control group). The frequency of A5.1-positive cases was also significantly increased in the patient group (68.0%) as compared with the controls (38.0%) (Pc < 0.0001). Furthermore, the carrier frequency of A5.1-positive was significantly increased in psoriatic patients with a positive family history and with early onset as compared with sporadic cases (Pc = 0.0005) and with late onset PS (Pc = 0.002)., Conclusions: These results suggest that the MICA gene may be associated with the development of PS in Chinese.

Objective: To determine the clinical features of psoriatic arthritis (PsA) in a multiethnic Oriental population and to study the effect of ethnicity on disease patterns., Methods: A retrospective study of 80 patients with PsA seen at either a rheumatology or dermatology referral center. Patients and case records were reviewed and data abstracted according to a standard protocol. Eighty consecutive patients with psoriasis without PsA seen at the dermatology center were recruited as controls., Results: Asymmetric polyarthritis developing in the 4th decade with an equal male to female ratio was the commonest pattern of arthritis among Chinese, Indians, and Malays. Clinically apparent lumbar spondylitis was significantly more common in Indians than Chinese (10/11 vs 11/20, respectively; p = 0.046), although the prevalence of lumbar spondylitis was similar in all ethnic groups. Eighty-nine percent of subjects required nonsteroidal antiinflammatory drugs and 51% required disease modifying antirheumatic drugs at some time for control of joint disease. PsA was significantly more common among Indians compared to the ethnic distribution of the Singapore population (p < 0.000001). Multiple logistic regression identified Indian ethnicity as a risk factor for the development of PsA (OR 2.39, 95% confidence interval 1.02 to 5.60)., Conclusion: The commonest pattern of PsA in all ethnic groups was asymmetric polyarthritis. Ethnicity affected the development and presentation of PsA in our series: Indians with psoriasis had double the risk of developing PsA compared to Chinese with psoriasis, and lumbar spondylitis when present in Chinese subjects was asymptomatic in 45%, being detectable only on radiological examination.