Variant analysis of CARD14 in a Chinese Han population with psoriasis vulgaris and generalized pustular psoriasis.
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ABSTRACT:
SUBMITTER: Qin P
PROVIDER: S-EPMC4227539 | biostudies-literature | 2014 Dec
REPOSITORIES: biostudies-literature
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Variant analysis of CARD14 in a Chinese Han population with psoriasis vulgaris and generalized pustular psoriasis.
Qin Peipei P Zhang Qilin Q Chen Mingfei M Fu Xi'an X Wang Chuan C Wang Zhenzhen Z Yu Gongqi G Yu Yongxiang Y Li Xiuyan X Sun Yonghu Y Wu Weizhi W Yang Baoqi B Liu Hong H Zhang Furen F
The Journal of investigative dermatology 20140707 12
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Project description:BackgroundGeneralized pustular psoriasis (GPP) is a rare and severe type of psoriasis. Previous studies have reported that metabolic syndrome and its components have been associated with psoriasis.ObjectiveTo investigate the association of metabolic syndrome-related single-nucleotide polymorphisms (SNPs) and GPP in Chinese Han population.Materials and methodsOne hundred and thirty-six (136) GPP patients and 965 healthy controls were recruited in the study. Approximately, 4 ml peripheral venous blood was collected from each participant. After collection, second-generation sequencing was used to detect genetic polymorphism of 15 SNPs. The plink 1.07 software package was used for statistical analysis.ResultsRs805303 (p = 0.01, OR = 0.70) and rs3177928 (p = 3.18E-07, OR = 2.66) in HLA were significantly different between the two groups. Moreover, rs4506565 (p = 1.41E-03, OR = 2.72) and rs7901695 (p = 9.39E-04, OR = 2.82) in TCF7L2 were significantly associated with GPP in patients without a previous history of PsV. Genotype analysis of rs4506565 and rs7901695 showed that under the recessive model, genotype frequencies of rs4506565 (p = 0.00, OR = 18.52) and rs7901695 (p = 0.00, OR = 18.44) were significantly different between GPP patients and healthy controls.ConclusionRs805303 and rs3177928 in HLA may increase the risk of GPP in the Chinese Han population. TCF7L2 may be a risk factor for GPP in patients without a previous history of PsV.
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Project description:BackgroundRecent mutation analysis identified several missense mutations in CARD14 in psoriasis.ObjectivesWe performed the genomic sequence analysis on CARD14 in southern Chinese Han Cantonese with Psoriasis Vulgaris (PsV) to reveal more causative missense mutations.MethodsA total of 131 patients with PsV and 207 matched controls were included. We conducted sequence analysis of all the exon and exon-intron boundaries of CARD14 in the group of PsV patients and subsequent case control analysis of potential sequence variants of significance.ResultsWe found five rare mutations and four of them are annotated or reported. Only the variant (c.1291C>G) has not been reported and annotated, but the variant was also found in controls. No significant difference was detected among all rare variant allele frequencies of patients and controls.ConclusionNone of the new definite variants were pathogenic. The other pathogenic mutations for PsV are still elusive in our cohort.
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Project description:Generalized pustular psoriasis (GPP) is a rare, severe form of pustular psoriasis characterized by widespread, recurrent episodes of neutrophil-rich pustule formation in the epidermis, which can be accompanied by fever and systemic inflammation. Recent clinical, histologic, and genetic evidence indicates that GPP is a distinct entity from plaque psoriasis, with different cytokine pathways predominant in the manifestation of each disease. The interleukin-36 (IL-36) signaling cascade plays a key role in regulating the innate immune system, and its dysregulation appears central to the pathogenesis of GPP. The altered expression of various IL-36 pathway constituents has been shown to cause a positive feedback loop of uncontrolled signaling and excess production of inflammatory cytokines, which in turn leads to chemokine induction and neutrophil recruitment in the epidermis. Given the potentially life-threatening nature of GPP episodes, drug interventions that rapidly achieve disease resolution are required. Early phase data indicate that treatments targeting various components of the IL-36 inflammatory cascade represent promising areas of research. However, there are currently no therapeutic agents specifically approved for GPP in the USA or Europe. Understanding the inflammatory pathways, associated risk factors, and role of neutrophils in the manifestation and perpetuation of GPP flares remains a key goal in developing effective therapeutics. In this article, we summarize the current understanding of GPP, describe novel therapeutic opportunities, and detail how the unique pathophysiology of the disease may inform future treatment strategies.
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2023-06-04 | E-MTAB-11144 | biostudies-arrayexpress
Project description:Psoriasis is a serious non-communicable, chronic immune-inflammatory mediated disease affecting about 125 million people worldwide. Its effects go beyond skin manifestation. Through genome-wide association studies, the caspase recruitment domain family member 14 (CARD14) gene and other gene variants have been implicated to have an association with Psoriasis, and as we move towards individualized therapy the discovery of single nucleotide polymorphism (SNP) is of great importance. This study aimed to determine whether the CARD14 gene is a susceptible gene for psoriasis vulgaris. In this study, 101 psoriasis patients and 79 healthy controls were subjected to exome sequencing. The CARD14 gene regions upstream and downstream of 1kb were sequenced. SNP-based association analysis and haplotype-based association analysis were performed in SNPs with minimum allele frequency (MAF) greater than 1%. Bioinformatic methods were used to predict the impact of risk loci on gene function. A total of 32 polymorphisms were identified in this study, of which 3 SNPs (1 in exon and 2 in intron) were susceptible to psoriasis (P < .05, OR = 0.19~0.53, 95%CI = 0.05~0.70). Bioinformatics analysis showed that rs144475004 located on the exon led to an amino acid change from aspartate to histidine. On the other hand, results of haplotype-based association analysis showed that 2 haplotypes (CARD14-1 and CARD14-2) were protective haplotypes of the disease (P < .05, OR = 0.18~0.38, 95%CI = 0.05~0.88), the frequencies in healthy controls and patients was 6.96% and 1.49%, respectively. CARD14 gene is associated with susceptibility to psoriasis vulgaris in the Hainan Han population.
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Project description:Generalized pustular psoriasis (GPP) is a severe disease featured by neutrophilic pustules and enhanced IL-36 inflammatory pathway in skin. Recently, a transcriptomic analysis of PBMCs and neutrophils in MPO-deficient GPP patients has been performed in stable disease state. However, transcriptomic profiling of PBMCs during acute flare of GPP is unclear. Here, we reported a predominant neutrophil signature in GPP PBMC and a marked increase in the CD66+CD16+ low-density neutrophils (LDNs) within the PBMC fraction of acute GPP patients. Transcriptomic and functional analysis of LDNs revealed a hypoinflammatory phenotype yet enhanced release of neutrophil granule proteases, implicating that LDNs might contribute to the IL-36-mediated inflammation in GPP patients.
2022-04-20 | GSE200977 | GEO
Project description:Psoriasis is a chronic inflammatory skin disease related to immune, whose complexity of molecular mechanisms is still not fully clear. RNA sequencing has been widely applied in various fields including biological medicine. According to the bioinformatics analysis of differential genes, biomarkers and drug targets have been discovered for the diagnosis and treatment of diseases. Besides, the pathological mechanisms of disease and functions of gene can be evaluated. In the present study, we report the application of RNA sequencing in skin tissues from psoriatic and healthy persons. By obtaining 2139 differential expressed genes (DEGs), 208 significantly differential GO terms and 44 significantly differential pathways were generated. We found that the functions of DEGs were mainly related to cell cycle, inflammatory, virus, immune response and metabolic process.The major pathways included cytokine-cytokine receptor interaction, Toll-like receptor signaling pathway, chemokine signaling pathway, cell cycle, metabolic pathways, ribosome, peroxisome, steroid biosynthesis and biosynthesis of unsaturated fatty acids. Furthermore, co-expression network was constructed to identify core genes and relations between genes. we considered genes with high values of degree and k-core difference in the co-expression network as core genes, such as IFNG, IL26, TLR3, PRKCQ, TLR4, CD274, CDK1 and IL17A. We chose CD274, an important immune checkpoint, to evaluate its regulatory mechanisms. Candidate genes related to CD274 were evaluated by the co-expression network analysis, and the relations between CD274 and candidate genes were validated in epidermal keratinocytes. Finally, IFNG and CDK1 inhibitor (indirubin) were found increasing the expression levels of CD274. In addition, indirubin was confirmed to attenuate mouse psoriasis-like skin lesion with the mechanisms related to CD274. In conclusion, this study provides us a comprehensive transcriptome analysis method on psoriasis to identify core genes and explore the important regulatory functions of genes.
2018-11-28 | GSE114286 | GEO
Project description:Psoriasis is a chronic immune-mediated inflammatory skin disease characterized by excessive proliferation of keratinocytes. It has a strong genetic predisposition; gene-gene interactions are important genetic models for common diseases. In this study, we explore pair-wise interactions among SNPs contributing to psoriasis susceptibility. We first performed gene interactions with exome-sequencing, next, we analyzed gene interactions combining the exome sequencing data with the targeted sequencing data. After we sequenced HLA region, we analyzed gene interactions including HLA regions and non-HLA regions. We found interactions between HLA regions were significant. We observed significant interactions between HLA-C*06:02 and rs118179173 (snp31443520; p = 8.21 × 10-20 , OR = 0.22) and between HLA-C*06:02 and HLA-B:AA67 (p = 1.22 × 10-12 , OR = 0.45). This study provides evidence that HLA is the most important susceptibility region on the risk of psoriasis and interactions that occur in this region are still significant.
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Project description:BackgroundPsoriasis is a common immune-mediated inflammatory dermatosis. Generalized pustular psoriasis (GPP) is the severe and rare type of psoriasis. The association between tumor necrosis factor-alpha induced protein 3 interacting protein 1 (TNIP1) gene and psoriasis was confirmed in people with multiple ethnicities. This study was to investigate the association between TNIP1 gene polymorphisms and pustular psoriasis in Chinese Han population.MethodsSeventy-three patients with GPP, 67 patients with palmoplantar pustulosis (PPP), and 476 healthy controls were collected from Chinese Han population. Six single nucleotide polymorphisms (SNPs) of the TNIP1 gene, namely rs3805435, rs3792798, rs3792797, rs869976, rs17728338, and rs999011 were genotyped by using polymerase chain reaction-ligase detection reaction. Statistical analyses were performed using the PLINK 1.07 package. Allele frequencies and genotyping frequencies for six SNPs were compared by using Chi-square test, odd ratio (OR) (including 95% confidence interval) were calculated. The haplotype analysis was conducted by Haploview software.ResultsThe frequencies of alleles of five SNPs were significantly different between the GPP group and the control group (P ≤ 7.22 × 10-3), especially in the GPP patients without psoriasis vulgaris (PsV). In the haplotype analysis, the most significantly different haplotype was H4: ACGAAC, with 13.1% frequency in the GPP group but only 3.4% in the control group (OR = 4.16, P = 4.459 × 10-7). However, no significant difference in the allele frequencies was found between the PPP group and control group for each of the six SNPs (P > 0.05).ConclusionsPolymorphisms in TNIP1 are associated with GPP in Chinese Han population. However, no association with PPP was found. These findings suggest that TNIP1 might be a susceptibility gene for GPP.
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