An in-depth analysis reveals two new genetic variants on 22q11.2 associated with vitiligo in the Chinese Han population.

BACKGROUND: Vitiligo is a complex disease in which patchy depigmentation is the result of an autoimmune-induced loss of melanocytes in affected regions. On the basis of a genome-wide linkage analysis of vitiligo in the Chinese Han population, we previously showed significant evidence of a linkage between 22q12 and vitiligo. Our aim in the current study was to identify vitiligo susceptibility variants within an expanded region of the 22q12 locus. METHODS AND RESULTS: An in-depth analysis of the expanded region of the 22q12 locus was performed by imputation using a large GWAS dataset consisting of 1117 cases and 1701 controls. Eight nominal SNPs were selected and genotyped in an independent cohort of Chinese Han individuals (2069 patients and 1370 control individuals) by using the Sequenom MassArray iPLEX1 system. The data were analyzed with PLINK 1.07 software. The C allele of rs730669 located in ZDHHC8/RTN4R showed a strong association with vitiligo (P = 3.25 × 10-8, OR = 0.81). The C allele of rs4820338 located in VPREB1 and the A allele of rs2051582 (a SNP reported in our previous study) located in IL2RB showed a suggestive association with vitiligo (P = 1.04 × 10-5, OR = 0.86; P = 1.78 × 10-6, OR = 1.27). The three identified SNPs showed independent associations with vitiligo in a conditional logistic regression analysis (all P < 1.0 × 10-5; all D' < 0.05 and r2 < 1.0 × 10-4). CONCLUSIONS: The study reveals that two novel variants rs730669 (ZDHHC8/RTN4R) and rs4820338 (VPREB1) on 22q11.2 might confer susceptibility to vitiligo and affect disease subphenotypes. The presence of multiple independent variants emphasizes their important roles in the genetic pathogenesis of disease.

Bach2 regulates aberrant activation of B cell in systemic lupus erythematosus and can be negatively regulated by BCR-ABL/PI3K.

OBJECTIVE: This study was aimed to explore the effect of Bach2 on B cells in systemic lupus erythematosus (SLE), as well as the underlying mechanisms. METHODS: Expression of Bach2, phosphorylated-Bach2 (p-Bach2), Akt, p-Akt and BCR-ABL (p210) in B cells isolated from SLE patients and the healthy persons were assessed by Western blot. Immunofluorescence staining was performed to assess the localization of Bach2 in B cells. Enzyme-linked immunosorbent assay (ELISA) was employed to detect IgG produced by B cells. Cell counting kit-8 (CCK-8) and Annexin-V FITC/PI double staining assay were adopted to evaluate cell proliferation and apoptosis in B cells, respectively. RESULTS: Compared to the healthy controls, Bach2, p-Akt and p210 were significantly decreased, while nuclear translocation of Bach2, IgG, CD40 and CD86 obviously up-regulated in B cells from SLE patients. Bach2 significantly inhibited the proliferation, promoted apoptosis of B cells from SLE patients, whereas BCR-ABL dramatically reversed cell changes induced by Bach2. Besides, BCR-ABL also inhibited nuclear translocation of Bach2 in B cells from SLE patients. Further, LY294002 treatment had no effect on decreased expression of Bach2 induced by BCR-ABL, but significantly eliminated BCR-ABL-induced phosphorylation of Bach2 and restored reduced nuclear translocation of Bach2 induced by BCR-ABL in B cells from SLE. CONCLUSIONS: Bach2 may play a suppressive role in B cells from SLE, and BCR-ABL may inhibit the nuclear translocation of Bach2 via serine phosphorylation through the PI3K pathway.

NFKB1 mediates Th1/Th17 activation in the pathogenesis of psoriasis.

This study was aimed to investigate whether NFKB1 participates in the pathogenesis of psoriasis by mediating Th1/Th17 cells. In this study, expression of NFKB1 was assessed in skin tissues from psoriasis patients and the healthy controls through Western blot and Immunohistochemistry. Enzyme-linked immunosorbent assay (ELISA) was used to analyze the serum levels of IFN-γ, IL-17 (IL-17A) and IL-17RA. The imiquimod-induced psoriasis mouse model was employed to examine the role of NFKB1 in psoriasis via the assessment of psoriasis area and severity index (PASI), including erythema, thickness and scales. The effects of NFKB1 on Th1/Th17 cells in were examined by flow cytometry. In vitro co-culture of Th1/Th17 cells isolated from different mice with HaCat cells was conducted to elucidate the effect of Th1/Th17 cells-mediated by NFKB1 on HaCat cells by MTT, wound healing and transwell invasion assay, respectively. The results showed that NF-κB p105/p50 expression in skin tissues was significantly increased in psoriasis (n = 21) compared to the healthy controls (n = 16), as well as levels of serum INF-γ and IL-17. Additionally, NF-κB p105/p50 expression in lesional skin tissues was much higher than that in non-lesional skin tissues of the same patients. In the psoriasis mouse model, NFKB1 overexpression significantly elevated the scores of erythema, thickness and scales. Besides, NFKB1 up-regulated the level of NF-κB p105/p50, INF-γ, T-bet, IL-17 and RORγt, as well as Th1/Th17 cells in skin tissues of psoriasis mice. Finally, in vitro assay confirmed that the activation of Th1 and Th17 mediated by NFKB1 in psoriasis promoted the proliferation, migration and invasion of keratinocytes. These findings suggest a critical role for NFKB1 in the regulation of Th1 and Th17 in psoriasis.

Association analyses identify two susceptibility loci 5q31 and 5q22.1 for atopic dermatitis in Chinese Han population.

BACKGROUND: Atopic dermatitis (AD) and other atopic diseases often share some common genetic and pathogenic bases. Recent genome-wide association studies (GWAS) have identified several loci associated with atopic diseases, allergic sensitization and asthma in different populations. The aim of this study was to investigate whether these susceptibility loci were related to AD in Chinese Han population. METHODS: Eight single nucleotide polymorphisms (SNPs) from recent atopic diseases and allergic sensitization GWAS were genotyped in 3,013 AD patients and 5,483 healthy controls in Chinese Han population using Sequenom MassArray system. Data was analyzed with PLINK 1.07 software. RESULTS: We identified that the susceptibility loci at 5q31 (RAD50/IL13, rs2158177, P = 1.08×10-3, OR = 1.15) and 5q22.1 (TSLP, rs1837253, P = 2.66×10-3, OR = 0.91) were significantly associated with AD. Genotype-based association testing revealed that the dominant model provided the best fit for both rs2158177 (P = 3.75×10-3) and rs1837253 (P = 5.30×10-3). Pathway analysis conformed that both loci were associated with the JAK-STAT signaling pathway. CONCLUSIONS: We identified two susceptibility loci 5q31 and 5q22.1 for AD that might bear candidate genes conferring susceptibility to AD.

Meta-analysis followed by replication identifies loci in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as associated with systemic lupus erythematosus in Asians.

Systemic lupus erythematosus (SLE) is a prototype autoimmune disease with a strong genetic involvement and ethnic differences. Susceptibility genes identified so far only explain a small portion of the genetic heritability of SLE, suggesting that many more loci are yet to be uncovered for this disease. In this study, we performed a meta-analysis of genome-wide association studies on SLE in Chinese Han populations and followed up the findings by replication in four additional Asian cohorts with a total of 5,365 cases and 10,054 corresponding controls. We identified genetic variants in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as associated with the disease. These findings point to potential roles of cell-cycle regulation, autophagy, and DNA demethylation in SLE pathogenesis. For the region involving TET3 and that involving CDKN1B, multiple independent SNPs were identified, highlighting a phenomenon that might partially explain the missing heritability of complex diseases.

Association of the chromosome 11p13.5 variant and atopic dermatitis with a family history of atopy in the Chinese Han population.

BACKGROUND: Recent genome-wide association studies (GWAS) and a meta-analysis of GWAS for atopic dermatitis (AD) have identified some AD genetic loci in European and Japanese populations. OBJECTIVE: To investigate whether some novel susceptibility loci are associated with AD in the Chinese Han population. METHODS: We first selected eight novel susceptibility loci to replicate in 2,205 AD patients and 2,116 healthy controls using the Sequenom platform. Data were analyzed with PLINK 1.07 software. RESULTS: We found that rs12634229 (3q13.2), rs7927894 (11p13.5) and rs878860 (11p15.4) showed a slight association with AD (P = 0.012, P = 0.033, P = 0.020, respectively); rs6780220 (3p21.33) was preferentially related to AD with keratosis pilaris, but did not reach the threshold of significance after correction. The frequency of rs7927894 allele T was significantly different between AD patients with a positive and negative family history of atopy. CONCLUSION: The loci rs7927894 (11p13.5) are related to AD with a positive family history of atopy in Chinese Han population, providing novel insight into the genetic pathogenesis of AD.

Association analysis revealed one susceptibility locus for vitiligo with immune-related diseases in the Chinese Han population.

Generalized vitiligo is an autoimmune disease characterized by melanocyte loss, which results in patchy depigmentation of skin and hair, and is associated with an elevated risk of other immune-related diseases. However, there is no reported study on the associations between immune susceptibility polymorphisms and the risk of vitiligo with immune-related diseases. The aim of this study was to evaluate the potential influence of 10 single-nucleotide polymorphisms (SNPs) at 18q21.31 (rs10503019), 4p16.1 (rs11940117), 3q28 (rs1464510), 14q12 (rs2273844), 12q13.2 (rs2456973), 16q12.2 (rs3213758), 10q25.3 (rs4353229), 3q13.33 (rs59374417), and 10p15.1 (rs706779 and rs7090530) on vitiligo with immune-related diseases in the Chinese Han population. All SNPs were genotyped in 552 patients with vitiligo-associated immune-related diseases and 1656 controls using the Sequenom MassArray system. Data were analyzed with PLINK 1.07 software. The C allele of rs2456973 at 12q13.2 was observed to be significantly associated with vitiligo-associated immune-related diseases (autoimmune diseases and allergic diseases) (P = 0.0028, odds ratio (OR) = 1.27). In subphenotype analysis, the rs2456973 C allele was also significantly associated with early-onset vitiligo by comparing with controls (P = 0.0001) and in the case-only analysis (P = 0.0114). We confirmed that 12q13.2 was an important candidate locus for vitiligo with immune-related diseases (autoimmune diseases and allergic diseases) and affected disease phenotypes with early onset.

Combined effect of five single nucleotide polymorphisms related to IL23/Th17 pathway in the risk of psoriasis.

Psoriasis is a common immune-mediated inflammatory skin disease with strong genetic components, in which the IL23/Th17 pathway has been implicated. To explore the effective role in psoriasis, we genotyped five single nucleotide polymorphisms in genes related to IL23/Th17 pathway in 14,929 Han Chinese samples. A Bonferroni-corrected significant single-variant association was identified between rs1512970 within IL21 (odds ratio (OR) = 1.07, 95 % confidence interval (CI) = 1.02-1.13, P = 4.94 × 10(-03)). We failed to validate rs744166 (OR = 1.06, 95 % CI = 1.01-1.11, P = 1.52 × 10(-02)) and other three SNPs (P = 2.48 × 10(-01) ∼ 1.27 × 10(-02)) to meet the single-variant association significance threshold. However, we found that their combined effect substantially contributed to the risk of psoriasis in our sample (P = 3.91 × 10(-07)) and the highest score group conferred the largest risk effect size (OR = 1.22, 95 % CI = 1.11-1.34, P = 1.85 × 10(-05)). Our results implicate the ethnic heterogeneity in the susceptibility of psoriasis and suggest common variants with weak effect in IL23/Th17 pathway, which do not show significance in conventional single-variant association study, may contribute to the risk of psoriasis. This study sheds light on the important role of IL23/Th17 pathway in the susceptibility of psoriasis.

EZH2 genetic variants affect risk of gastric cancer in the Chinese Han population.

Enhancer of zeste 2 (EZH2) gene encodes a histone methyltransferase that constitutes the catalytic component of the polycomb repressive complex-2 (PRC2) to initiate epigenetic silencing of genes. It is reported that the expression level of EZH2 in gastric cancer tissue was highly correlated with tumor progression, however, whether EZH2 genetic variants were associated with the risk of gastric cancer remains yet unknown. In this study, we conducted a genotyping analysis for EZH2 in 311 cases of gastric cancer and 425 controls from the Chinese Han population. We found five single nucleotide polymorphisms (SNP; rs12670401, rs6464926, rs2072407, rs734005, and rs734004) of EZH2 gene were significantly associated with the risk of gastric cancer. Of which, the rs12670401 with the minor allele C and rs6464926 with the minor allele T revealed strong associations with increased gastric cancer risk [P = 0.009, adjusted odds ratio (aOR) = 1.327, 95% CI = 1.075-1.683 and P = 0.012, aOR = 1.310, 95% CI = 1.059-1.619]. The other three SNPs, rs2072407, rs734005, and rs734004 contributed to significantly reduced risk of gastric cancer (P = 0.033, aOR = 0.787, 95% CI = 0.633-0.981, P = 0.045, aOR = 0.799, 95% CI = 0.642-0.995 and P = 0.048, aOR = 0.803, 95% CI = 0.645-0.999), respectively. We further found that rs12670401 and rs6464926 were in a strong LD while rs2072407, rs734005, and rs734004 were in another. Haplotype analysis of the five SNPs showed that haplotype CCTCT reduced the risk of gastric cancer (P = 0.031 and aOR = 0.784), while haplotype GTCTC significantly elevated the risk of gastric cancer (P = 0.011 and aOR = 1.310). We concluded that EZH2 variants were significantly associated with gastric cancer risk. Our results for the first time provided new insight into susceptibility factors of EZH2 gene variants in carcinogenesis of gastric cancer of the Chinese Han population.

Association analyses identifying two common susceptibility loci shared by psoriasis and systemic lupus erythematosus in the Chinese Han population.

BACKGROUND: Genome-wide association studies (GWASs) have revealed a large number of genetic risk loci for many autoimmune diseases. One clear finding emerging from the published genetic studies of autoimmunity is that different autoimmune diseases, such as psoriasis and systemic lupus erythematosus (SLE), share susceptibility loci. Our study explores additional susceptibility loci shared by psoriasis and SLE in the Chinese Han population. METHODS: In total, 20 single nucleotide polymorphisms (SNPs) in 17 previously reported psoriasis susceptibility loci and 34 SNPs from 24 previously reported SLE susceptibility loci were investigated in our initial psoriasis and SLE GWAS dataset. Among these SNPs, we selected two SNPs (rs8016947 and rs4649203) with association values of p<5×10(-2) for both diseases in the GWAS data for further investigation in psoriasis (7260 cases and 9842 controls) and SLE (2207 cases and 9842 controls) using a Sequenom MassARRAY system. RESULTS: We found that these two SNPs (rs8016947 and rs4649203) in two loci (NFKBIA and IL28RA) were associated with psoriasis and SLE with genome-wide significance (Pcombined<5×10(-8) in psoriasis and Pcombined<5×10(-8) in SLE): rs8016947 at NFKBIA (Pcombined-psoriasis=3.90×10(-10), Pcombined-SLE=1.08×10(-13)) and rs4649203 at IL28RA (Pcombined-psoriasis=3.91×10(-12), Pcombined-SLE=9.90×10(-9)). CONCLUSIONS: These results showed that two common susceptibility loci (NFKBIA and IL28RA) are shared by psoriasis and SLE in the Chinese Han population.

Variants in TNFSF4, TNFAIP3, TNIP1, BLK, SLC15A4 and UBE2L3 interact to confer risk of systemic lupus erythematosus in Chinese population.

Our previous genome-wide association studies on SLE have identified several susceptibility genes involved in NF-κB signaling pathway, including TNFSF4, TNFAIP3, TNIP1, BLK, SLC15A4 and UBE2L3. The aim of this study is to investigate the association model (additive, dominant, recessive) of these genes and search for possible gene-gene interactions between them. In this study, we explored the association model of these six genes and search for possible gene-gene interactions based on identified single-nucleotide polymorphisms (SNPs) among them by using logistic regression analysis in the combined sample of 4,199 cases and 8,255 controls. The most significant association evidence was observed under recessive model for all of these SNPs. Besides, significant interactions between these SNPs were observed in this study: the TNFSF4 and TNIP1 SNPs (P adjusted = 1.68E-10), the TNFSF4 and SLC15A4 SNPs (P adjusted = 3.55E-08), the TNFSF4 and UBE2L3 SNPs (P adjusted = 8.74E-13), the TNIP1 and BLK SNPs (P adjusted = 9.45E-10), the TNIP1 and UBE2L3 SNPs (P adjusted = 8.25E-11), the TNFAIP3 and UBE2L3 SNPs (P adjusted = 3.06E-14) and the BLK and SLC15A4 SNPs (P adjusted = 4.51E-12). These results may contribute to our understanding of SLE genetic interactions and account for the additional risk of certain patients to develop SLE.

Identification of Coding Variants in 10q22.1 Associated with Vitiligo in the Chinese Han Population.

Objective: This study aims to identify causal variants associated with vitiligo in an expanded region of 10q22.1. Materials and Methods: We conducted a fine-scale deep analysis of the expanded 10q22.1 region using in a large genome-wide association studies dataset consisting of 1117 cases and 1701 controls through imputation. We selected five nominal coding single nucleotide polymorphisms (SNPs) located in SLC29A3 and CDH23 and genotyped them in an independent cohort of 2479 cases and 2451 controls in a Chinese Han population cohort using the Sequenom MassArray iPLEX1 system. Results: A missense SNP in SLC29A3, rs2252996, showed strong evidence of association with vitiligo (p = 1.34 × 10-8, odds ratio [OR] = 0.82). Three synonymous SNPs (rs1084004 in SLC29A3; rs12218559 and rs10999978 in CDH23) provided suggestive evidence of association for vitiligo (p = 1.69 × 10-6, OR = 0.84; p = 9.47 × 10-5, OR = 1.18; p = 6.90 × 10-4, OR = 1.16, respectively). Stepwise conditional analyses identified two significant independent disease-associated signals from the four SNPs (both p < 0.05; both D' = 0.03; and r2 = 0.00). Conclusion: The study identifies four genetic coding variants in SLC29A3 and CDH23 on 10q22.1 that may contribute to vitiligo susceptibility with one missense variant affecting disease subphenotypes. The presence of multiple genetic variants underscores their significant role in the genetic pathogenesis of the disease.

Exome sequencing identified a missense mutation of EPS8L3 in Marie Unna hereditary hypotrichosis.

BACKGROUND: Marie Unna hereditary hypotrichosis (MUHH) is an autosomal dominant disorder characterised by coarse, wiry, twisted hair developed in early childhood and subsequent progressive hair loss. MUHH is a genetically heterogeneous disorder. No gene in 1p21.1-1q21.3 region responsible for MUHH has been identified. METHODS: Exome sequencing was performed on two affected subjects, who had normal vertex hair and modest alopecia, and one unaffected individual from a four-generation MUHH family of which our previous linkage study mapped the MUHH locus on chromosome 1p21.1-1q21.3. RESULTS: We identified a missense mutation in EPS8L3 (NM_024526.3: exon2: c.22G->A:p.Ala8Thr) within 1p21.1-1q21.3. Sanger sequencing confirmed the cosegregation of this mutation with the disease phenotype in the family by demonstrating the presence of the heterozygous mutation in all the eight affected and absence in all the seven unaffected individuals. This mutation was found to be absent in 676 unrelated healthy controls and 781 patients of other disease from another unpublished project of our group. CONCLUSIONS: Taken together, our results suggest that EPS8L3 is a causative gene for MUHH, which was helpful for advancing us on understanding of the pathogenesis of MUHH. Our study also has further demonstrated the effectiveness of combining exome sequencing with linkage information for identifying Mendelian disease genes.

Exome sequencing identifies a COL14A1 mutation in a large Chinese pedigree with punctate palmoplantar keratoderma.

BACKGROUND: Punctate palmoplantar keratoderma (PPPK) is a rare autosomal dominant skin disorder characterised by numerous hyperkeratotic papules irregularly distributed on the palms and soles. To date, no causal gene for this disease has been identified. METHODS: We performed exome sequencing analysis of four affected individuals and two unaffected controls from one Chinese PPPK family where disease locus was mapped at 8q24.13-8q24.21 by our previous linkage analysis. RESULTS: We identified a novel heterozygous mutation in COL14A1 gene (c.4505C→T (p.Pro1502Leu)), which located within the linkage region that we previously identified for PPPK. The mutation was shared by the four affected individuals, but not for the two controls of the family. Sanger sequencing confirmed this mutation in another four cases from this family. This mutation was invisible in the normal controls of this family as well as the additional 676 unrelated normal controls and 781 patients with other disease. The shared COL14A1 mutation, p.Pro1502Leu, is a missense substitution at a highly conserved amino acid residue across multiple species. CONCLUSIONS: The power of combining exome sequencing and linkage information in the study of genetics of autosomal dominant disorders, even in simplex cases, has been demonstrated. Our results suggested that COL14A1 would be a casual gene for PPPK, which was helpful for advancing us on understanding of the pathogenesis of PPPK.

Application of a flipped classroom teaching model based on micro-videos in the standardized training of dermatological residents in China.

Objective: To explore the effects of a micro-video-based flipped classroom teaching model on the standardized training of dermatological residents in China. Methods: A total of 78 residents who had received standardized training at the Department of Dermatology of the First Affiliated Hospital of Anhui Medical University were selected and randomly divided into an experimental group (39 residents) and a control group (39 residents). The experimental group received micro-video-based flipped classroom teaching, whereas the control group received traditional lecture-based classroom teaching. Scores relating to theoretical knowledge of dermatology, clinical practice skills, and the results of a questionnaire survey were used to evaluate the teaching effects. Results: The average score of the experimental group in the theoretical knowledge test (88.56 ± 5.80) was significantly higher than that of the control group (81.90 ± 7.45). Similarly, the average score of the experimental group in the clinical practice skills test (85.44 ± 5.97) was also significantly higher than that of the control group (78.46 ± 5.94). The results of the questionnaire survey showed that the experimental group exhibited significant improvements in learning interest, mastery of teaching content, communication skills, expression skills, clinical practice skills, autonomous learning, clinical thinking, clinical application, and team cooperation. Conclusion: Flipped classroom teaching based on micro-videos helped to improve the teaching effects of theoretical knowledge, clinical practice skills, and residents' comprehensive ability during dermatological residents' standardized training.

E-selectin rs5361 and FCGR2A rs1801274 variants were associated with increased risk of gastric cancer in a Chinese population.

Host immune responses are critical steps for carcinogenesis. Single nucleotide polymorphisms (SNPs) in immunoregulatory genes may influence gastric cancer risk. We performed a genotyping analysis for immunoregulatory genes in 311 gastric cancer cases and 425 controls from a Chinese population. We found that there were significant differences of E-selectin variant rs5361 (A>C) and FCGR2A variant rs1801274 (T>C) between cases and controls (P = 0.022 and P = 0.0001, respectively). Logistic regression analysis indicated that genotype of E-selectin rs5361AC increased the risk of gastric cancer significantly (P = 0.026, adjusted Odds ratio (OR) = 2.84, 95% confidence interval (CI) = 1.13-7.12). C allele of E-selectin rs5361 showed a significant increased frequency in cases (P = 0.023). However, the E-selectin variant did not affect the protein expression. E-selectin protein was observed not only in tumor interstitial vascular endothelial cells, but also in gastric cancer cells at primary and metastatic sites. The protein was associated with clinicopathological characteristics of gastric cancer, such as age (P = 0.008), tumor size (P = 0.027), differentiation (P = 0.000), and tumor-node-metastasis (TNM) stage (P = 0.006). CT and CC + CT genotypes of FCGR2A variant rs1801274 increased gastric cancer risk (P = 0.000, adjusted OR = 1.92, 95%CI = 1.36-2.72; P = 0.003, adjusted OR = 1.68, 95%CI = 1.20-2.35, respectively). Interleukin-4 receptor (IL-4R) variant rs2107356 presented negative correlations to E-selectin variant rs5361 and FCGR2A variant rs1801274 (P = 0.035 and P = 0.023) in conferring susceptibility to gastric cancer. We concluded E-selectin variant rs5361 and FCGR2A variant rs1801274 were significantly associated with gastric cancer risk. Expression of E-selectin protein would promote progression of gastric cancer.

Meta-analysis of NOD2/CARD15 polymorphisms with psoriasis and psoriatic arthritis.

Psoriasis and psoriatic arthritis (PsA) is a complex autoimmune disease. NOD2/CARD15 gene has been suggested to play an important role in the pathogenesis of psoriasis and PsA. This study aims to assess the association between NOD2/CARD15 polymorphisms and the susceptibility to psoriasis/PsA. A meta-analysis was performed to survey studies on the NOD2/CARD15 polymorphisms and psoriasis/PsA using comprehensive PubMed, Embase, and Web of Science citation search. A total of 9 published studies were involved. Meta-odds ratios (ORs) and 95% confidence intervals (CIs) based on fixed effects models or random effects models were depended on Cochran's Q-statistic. Potential publication bias was evaluated by Egger's linear regression test. As for R702W, the pooled ORs were 1.041 (95% CI 0.854-1.268, P = 0.693; 2,081 patients vs. 2,717 controls) for C allele and 0.886 (95% CI 0.565-1.391. P = 0.600; 1,222 patients vs. 1,818 controls) for genotype. Then for G908R, the pooled ORs were 1.042 (95% CI, 0.761-1.426, P = 0.799; 2,053 patients vs. 2,743 controls) for C allele and 0.942 (95% CI 0.708-1.254, P = 0.683; 1,226 patients vs. 1,824 controls) for the homozygous wild type. Then for Leu1007fsinsC allele polymorphism and genotype, the pooled ORs were 1.160 (95% CI, 0.893-1.507, P = 0.266; 2,279 patients vs. 3,067 controls) and 1.266 (95% CI 0.897-1.789, P = 0.180; 1,979 patients vs. 1,607 controls), respectively. No obvious publication bias was shown in the results. The association between NOD2/CARD15 polymorphisms and psoriasis/PsA was not found. Taken together, our results suggest that NOD2/CARD15 might not be a susceptibility gene for psoriasis and psoriatic arthritis.

Case report: Infantile generalized pustular psoriasis with IL36RN and CARD14 gene mutations.

Infantile pustular psoriasis (IPP) is an extremely rare skin disease associated with genetic factors. Gene mutations of IL36RN (interleukin-36 receptor antagonist), CARD14 (caspase recruitment family member 14), and AP1S1 (the σ1C subunit of the adaptor protein complex 1) had been identified to be involved in the pathogenesis of IPP. IPP usually develops with no preceding psoriasis vulgaris (PV) or familial history. Here, we report a case of a 6-month-old infant and make the diagnosis of IPP by a series of examinations; subsequently, by detecting coexistent mutations of IL36RN and CARD14, the diagnosis is intensified from a genetic point of view. We treated the child with traditional oral and topical drugs regardless of the commonly used acitretin considering its potential side effects, such as skeletal toxicity, and the lesions got conspicuous improvement with much reduction of inflammation. Owing to the genetic mutation of IL-36, there had been reported cases focusing on anti-IL36 biological agents in the treatment of IPP, and it could be a new weapon to treat and improve such IL-36RN-deficient skin diseases.