Risk Factor For Psoriasis Research Articles

Key genes and immune infiltration patterns and the clinical implications in psoriasis patients.

Psoriasis is an immune-mediated skin disease, closely related to immune regulation. The aim was to understand the pathogenesis of psoriasis further, reveal potential therapeutic targets, and provide new clues for its diagnosis, treatment, and prevention. Expression profiling data were obtained from the Gene Expression Omnibus (GEO) database for skin tissues from healthy population and psoriasis patients. Differentially expressed genes (DEGs) were selected for Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) analysis separately. Machine learning algorithms were used to obtain characteristic genes closely associated with psoriasis. Receiver operating characteristic (ROC) curve was used to assess the diagnostic value of the characteristic genes for psoriasis. The Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) algorithm was used to calculate the proportion of immune cell infiltration. Correlation analysis was used to characterize the connection between gene expression and immune cell, Psoriasis Area and Severity Index (PASI). A total of 254 DEGs were identified in the psoriasis group, including 185 upregulated and 69 downregulated genes. GO was mainly enriched in cytokine-mediated signaling pathway, response to virus, and cytokine activity. KEGG was mainly focused on cytokine-cytokine receptor interaction and IL-17 signaling pathway. GSEA was mainly in chemokine signaling pathway and cytokine-cytokine receptor interaction. The machine learning algorithm screened nine characteristic genes C10orf99, GDA, FCHSD1, C12orf56, S100A7, INA, CHRNA9, IFI44, and CXCL9. In the validation set, the expressions of these nine genes increased in the psoriasis group, and the AUC values were all>0.9, consistent with those of the training set. The immune infiltration results showed increased proportions of macrophages, T cells, and neutrophils in the psoriasis group. The characteristic genes were positively or negatively correlated to varying degrees with T cells and macrophages. Nine characteristic genes were highly expressed in the moderate to severe psoriasis group and positively correlated with PASI scores. High levels of nine characteristic genes C10orf99, GDA, FCHSD1, C12orf56, S100A7, INA, CHRNA9, IFI44, and CXCL9 were risk factors for psoriasis, the differential expression of which was related to the regulation of immune system activity and PASI scores, affecting the proportions of different immune cells and promoting the occurrence and development of psoriasis.

High level of gamma-glutamyltransferase is a possible risk factor for psoriasis: A nationwide population-based cohort study.

Background Gamma-glutamyl transferase (GGT) has been associated with coronary heart disease, diabetes mellitus, and hypertension, but its association with psoriasis has not yet been elucidated. Aims We conducted this study to determine the association between the risk of psoriasis and the serum GGT. Methods We conducted a nationwide population-based study. A total of 9,939,350 people met the enrolment criteria. The study population was classified into four groups based on GGT levels and the risk of psoriasis was calculated for each group. Results The incidence rates of psoriasis per 1,000 person-years were 2.96105 and 3.68577 in the lowest and highest GGT groups, respectively. After adjusting for age, sex, income, diabetes mellitus, hypertension, dyslipidemia, smoking, alcohol intake, exercise, and body mass index, the highest GGT group showed a significantly increased risk of developing psoriasis (hazard ratio: 1.057, 95% confidence interval: 1.044-1.07). This risk of psoriasis was significantly higher among the old age group (hazard ratio: 1.162, 95% confidence interval: 1.128-1.197) and women (hazard ratio: 1.14, 95% confidence interval: 1.117-1.164). Limitations The limitations of this study included the retrospective design, International Classification of Diseases code-based diagnosis, small hazard ratio, and non-availability of data on covariates. Conclusion The GGT level was found to be an independent risk factor for developing psoriasis.

Association between chronic renal disease and psoriasis risk in diabetes patients: A Korean population-based study.

Background Several studies have reported that psoriasis has a positive correlation with type 2 diabetes mellitus (DM). Understanding the risk of psoriasis in diabetic patients is significant because it allows for early intervention and potential insights into the common pathways between the two conditions. Objectives We analysed the risk of psoriasis according to the estimated glomerular filtration rate (eGFR) and proteinuria level in DM patients using Korean population-based data. Methods This study was a retrospective cohort study using data collected from the country in the form of exploratory data analysis. A total of 927,234 participants diagnosed with DM were enrolled. Patients under the age of 20 with existing psoriasis or psoriasis developed within 1 year and missing data were excluded. The development of psoriasis was the primary outcome within a follow-up period of 7.83 ± 1.68 years. Results Of the 840,395 final participants, 28,010 (3.33%) patients developed psoriasis. In multivariate-adjusted Cox proportional hazards regression models, the DM patients with eGFR < 30 had a higher risk of psoriasis after adjustment (eGFR 60-90, hazard ratio [HR] 1 (Ref.); eGFR < 30, HR 1.173, 95% CI 1.089-1.264). In addition, there was an increased psoriatic risk of patients with DM and proteinuria after adjustment (negative, HR 1 (Ref.); 2+, HR 1.164, 95% CI 1.080-1.254; 3+, HR 1.433, 95% CI 1.273-1.613; 4+, HR 1.508, 95% CI 1.177-1.931). Limitations The severity of psoriasis was not measured since the occurrence of psoriasis was the outcome. Details of oral hypoglycaemic agents such as type and dose were not investigated. Conclusion This study showed that a decrease in eGFR and aggravation of proteinuria increase the risk of psoriasis in diabetic patients. Therefore, by using eGFR and proteinuria as predictive risk factors of psoriasis in DM patients, early and proactive treatment may play a vital role in managing diabetic patients.

Genetic Study of Psoriasis Highlights its Close Link with Socioeconomic Status and Affective Symptoms

Psoriasis is an inflammatory skin disease with an estimated heritability of around 70 %. Previous genome-wide association studies (GWASs) have detected several risk loci for psoriasis. To further improve the understanding of the genetic risk factors impacting the disease, we conducted a discovery GWAS in FinnGen and a subsequent replication and meta-analysis with data from the Estonian Biobank and the UK biobank; the study sample included 925 649 individuals (22 659 cases and 902 990 controls), the largest sample for psoriasis yet. In addition, we conducted downstream analyses to find out more about psoriasis’ cross-trait genetic correlations and causal relationships. We report 6 risk loci to our knowledge previously unreported, most of which harbor genes related to nuclear factor kappa-light-chain-enhancer of activated B-cells-signaling pathway and overall immunity. Genetic correlations highlight the relationship between psoriasis and smoking, higher body weight, and lower education level. Additionally, we report causal relationships between psoriasis and mood symptoms, as well as two-directioned causal relationship between psoriasis and lower education level. Our results provide further knowledge on psoriasis risk factors, which may be useful in the development of future treatment strategies.

Effect of smoking cessation on psoriasis vulgaris, palmoplantar pustulosis and generalized pustularpsoriasis.

Smoking is a known risk factor for psoriasis; however, the impact of smoking cessation on psoriasis has seldom been evaluated. We aimed to examine the effects of smoking cessation on the development of psoriasis vulgaris (PsV), palmoplantar pustulosis (PPP) and generalized pustular psoriasis (GPP). Using the Korean National Health Insurance Service database, we retrospectively compiled a cohort of 5 784 973 participants without psoriasis, analysed their changes in smoking status from 2004 to 2007 and followed up new cases of psoriasis until 2021. The psoriasis risks were compared with those of sustained smokers, smoking quitters, sustained ex-smokers and never smokers using multivariate Cox proportional hazard models. The mean age of the participants was 47.1 years (SD 13.5) and 3 092 426 (53.5%) were male. During 77 990 688 person-years, 67 364 psoriasis cases were identified. Compared with sustained smokers, smoking quitters showed a reduced risk of developing psoriasis [adjusted hazard ratio (aHR) 0.91; 95% confidence interval (CI) 0.87-0.95], specifically PsV (aHR 0.92; 95% CI 0.88-0.97) and PPP (aHR 0.71; 95% CI 0.63-0.79). The reduction in risk due to smoking cessation was more prominent in sustained ex-smokers (psoriasis: aHR 0.77, 95% CI 0.74-0.79; PsV: aHR 0.76, 95% CI 0.73-0.79; PPP: aHR 0.56, 95% CI 0.51-0.61; GPP: aHR 0.64; 95% CI 0.52-0.78). When conducting sensitivity analyses to address the potential for changes in smoking habits after 2007, the results and trends were consistent with the main findings, and a more pronounced significance was observed. Compared with continuous smoking, smoking cessation was associated with a decreased risk of developing psoriasis. The risk-reducing effect of smoking cessation was more pronounced in those maintaining a smoke-free status. Smoking cessation and the maintenance of a smoke-free status should be encouraged to prevent the development of psoriasis and all other smoking-related diseases.

Causal associations between both psoriasis and psoriatic arthritis and multiple autoimmune diseases: a bidirectional two-sample Mendelian randomization study.

Numerous observational studies have identified associations between both psoriasis (PsO) and psoriatic arthritis (PsA), and autoimmune diseases (AIDs); however, the causality of these associations remains undetermined. We conducted a bidirectional two-sample Mendelian Randomization study to identify causal associations and directions between both PsO and PsA and AIDs, such as systemic lupus erythematosus (SLE), Crohn's disease (CD), ulcerative colitis (UC), multiple sclerosis (MS), uveitis, bullous pemphigoid (BP), Hashimoto's thyroiditis (HT), rheumatoid arthritis (RA), vitiligo, and ankylosing spondylitis (AS). The causal inferences were drawn by integrating results from four regression models: Inverse Variance Weighting (IVW), MR-Egger, Weighted Median, and Maximum Likelihood. Furthermore, we performed sensitivity analyses to confirm the reliability of our findings. The results showed that CD [IVW odds ratio (ORIVW), 1.11; 95% confidence interval (CI), 1.06-1.17; P = 8.40E-06], vitiligo (ORIVW, 1.16; 95% CI, 1.05-1.28; P = 2.45E-03) were risk factors for PsO, while BP may reduce the incidence of PsO (ORIVW, 0.91; 95% CI, 0.87-0.96; P = 1.26E-04). CD (ORIVW, 1.07; 95% CI, 1.02-1.12; P = 0.01), HT (ORIVW, 1.23; 95% CI, 1.08-1.40; P = 1.43E-03), RA (ORIVW, 1.11; 95% CI, 1.02-1.21, P = 2.05E-02), AS (ORIVW, 2.18; 95% CI, 1.46-3.27; P = 1.55E-04), SLE (ORIVW, 1.04; 95% CI, 1.01-1.08; P = 1.07E-02) and vitiligo (ORIVW, 1.27; 95% CI, 1.14-1.42; P = 2.67E-05) were risk factors for PsA. Sensitivity analyses had validated the reliability of the results. Our study provides evidence for potential causal relationships between certain AIDs and both PsO and PsA. Specifically, CD and vitiligo may increase the risk of developing PsO, while CD, HT, SLE, RA, AS, and vitiligo may elevate the risk for PsA. Additionally, it is crucial to closely monitor the condition of PsO patients with specific AIDs, as they have a higher likelihood of developing PsA than those without AIDs. Moving forward, greater attention should be paid to PsA and further exploration of other PsO subtypes is warranted.

Risk Factors for Psoriasis Flares: A Narrative Review.

Psoriasis is a chronic inflammatory cutaneous disease with multifactorial pathogenesis involving both genetic and environmental factors as well as the innate and acquired immune response. Several triggering factors may exacerbate or worsen the disease. In this context, we performed a review manuscript with the aim of investigating current literature on psoriasis risk factors, also showing possible mechanisms by which they act on psoriasis. Globally, risk factors can be divided in classic risk factors (eg, mechanical stress, infections and dysbiosis of the skin, common drugs, environment and pollution, lifestyle, psychological stress, hormonal and metabolic alterations) which have long been known to be responsible for worsening and/or reoccurrence of psoriatic manifestations, and emerging risk factors (eg, biological drugs, immunotherapy for oncologic disease, Covid-19, and vaccines) defined as those newly identified risk factors. Accurate patient information and monitoring of risk factors as well as planned follow-ups may help to prevent and treat the worsening of psoriasis and consequently improve the quality of life of psoriatic patients.

The association between ACE inhibitors and psoriasis based on the drug-targeted Mendelian randomization and real-world pharmacovigilance analyses

ABSTRACT Background Although a growing number of observational studies suggest that angiotensin-converting enzyme inhibitors (ACEIs) intake may be a risk factor for psoriasis, evidence is still insufficient to draw definitive conclusions. Research design and methods Drug-targeted Mendelian randomization (DTMR) was used to analyze the causality between genetic proxied ACEIs and psoriasis. Furthermore, we performed a disproportionality analysis based on the FDA adverse event reporting system (FAERS) database to identify more suspicious subclasses of ACEIs. Results Using two kinds of genetic proxy instruments, the present DTMR research identified genetic proxied ACEIs as risk factors for psoriasis. Furthermore, our disproportionality analysis revealed that ramipril, trandolapril, perindopril, lisinopril, and enalapril were associated with the risk of psoriasis, which validates and refines the findings of the DTMR. Conclusions Our integrative study verified that ACEIs, especially ramipril, trandolapril, perindopril, lisinopril, and enalapril, tended to increase the risk of psoriasis statistically.

Cholesterol and low-density lipoprotein as a cause of psoriasis: Results from bidirectional Mendelian randomization.

Psoriasis is an inflammatory disease that affects many people. However, the causal effect of lipid metabolism on psoriasis has not yet been verified. This study aimed to identify the genetic relationship between serum lipid levels and psoriasis. Bidirectional two-sample Mendelian randomization (MR) was used to analyse the causal relationship between cholesterol and psoriasis. The outcome of the forward causality test was psoriasis. In the analysis of reverse causality, psoriasis was exposed, and 79 single-nucleotide polymorphisms were detected in the genome-wide association study (GWASs) database from the IEU GWASs Project. MR-Egger regression, inverse variance-weighted, weighted median, weighted mode and simple mode were used for the MR analyses. The level of triglyceride, lipase member N, chylomicrons, extremely large very low-density lipoprotein (VLDL) particles, high-density lipoprotein (HDL) cholesterol levels, cholesterol esters in large HDL, cholesterol esters in medium HDL and cholesterol esters in medium VLDL have not affected the development of psoriasis. However, total cholesterol, total free cholesterol, low-density lipoprotein (LDL) cholesterol levels, cholesterol esters in large VLDL and cholesterol esters in medium LDL were unidirectional causal effects on psoriasis. Bidirectional two-sample MR analysis indicated that high levels of total cholesterol, total free cholesterol, LDL cholesterol, cholesterol esters in large VLDL and cholesterol esters in medium LDL are genetic risk factors for psoriasis.

HLA-Cw6 increases the risk of psoriasis and early onset before twenty-seven years of age among the Vietnamese population.

Psoriasis is a chronic inflammatory skin disease that affects people all over the world. It is linked to the HLA-Cw6 allele, which is more common in Caucasians than in Asians and varies across ethnic groups. We investigated the association between the disease severity and the onset age of HLA-Cw6 prevalence in Vietnamese psoriasis patients. In 121 psoriasis patients and 30 healthy controls, we looked at the relationship between HLA-Cw6 and clinical features. We found that patients with psoriasis had significantly higher levels of HLA-Cw6 (64.5%) than controls (26.7%) (p=0.0001), with an odds ratio of 4.98 (2.04-12.15). Positive HLA-Cw6 patients had a significantly lower mean age of psoriasis onset than negative HLA-Cw6 patients. Patients with mild psoriasis (100%) were more likely to have the AA genotype, while patients with moderate to severe psoriasis (47.2% and 59.0%, respectively) and those with high PASI scores (55.1% and 54.1%, respectively) were more likely to have the TA genotype. Thus, HLA-Cw6 is a major genetic risk factor for psoriasis in Vietnamese patients, especially early-onset cases. Variations in HLA-Cw6 genotypes also affect disease severity.

Causal Associations Between Gut Microbiota and Psoriasis: A Mendelian Randomization Study.

Previous studies have proposed a possible gut-skin axis, and linked gut microbiota to psoriasis risks. However, there is heterogeneity in existing evidence. Observational research is prone to bias, and it is hard to determine causality. Therefore, this study aims to evaluate possible causal associations between gut microbiota (GM) and psoriasis. With published large-scale GWAS (genome-wide association study) summary datasets, two-sample Mendelian randomization (MR) was performed to sort out possible causal roles of GM in psoriasis and arthropathic psoriasis (PsA). The inverse variance weighted (IVW) method was taken as the primary evaluation of causal association. As complements to the IVW method, we also applied MR-Egger, weighted median. Sensitivity analyses were conducted using Cochrane's Qtest, MR-Egger intercept test, MR-PRESSO (Mendelian Randomization Pleiotropy RESidual Sum and Outlier) global test, and leave-one-out analysis. By primary IVW analysis, we identified nominal protective roles of Bacteroidetes (odds ratio, OR0.81, P = 0.033) and Prevotella9 (OR0.87, P = 0.045) in psoriasis risks. Bacteroidia (OR0.65, P = 0.03), Bacteroidales (OR0.65, P = 0.03), and Ruminococcaceae UCG002 (OR0.81, P = 0.038) are nominally associated with lower risks for PsA. On the other hand, Pasteurellales (OR1.22, P = 0.033), Pasteurellaceae (OR1.22, P = 0.033), Blautia (OR1.46, P = 0.014), Methanobrevibacter (OR1.27, P = 0.026), and Eubacterium fissicatena group (OR1.21, P = 0.028) are nominal risk factors for PsA. Additionally, E.fissicatena group is a possible risk factor for psoriasis (OR1.22, P = 0.00018). After false discovery rate (FDR) correction, E.fissicatena group remains a risk factor for psoriasis (PFDR = 0.03798). We comprehensively evaluated possible causal associations of GM with psoriasis and arthropathic psoriasis, and identified several nominal associations. E.fissicatena group remains a risk factor for psoriasis after FDR correction. Our results offer promising therapeutic targets for psoriasis clinical management.

Serum level of certain cytokines associated with psoriasis progression in Iraqi patients

Introduction and Aim: Psoriasis is a skin ailment that typically affects the scalp, lower back, knees, elbows, and results in flaky skin patches. The purpose of this study was to compare cytokines, leptin, and adiponectin levels, as well as several physiological characteristics, in psoriasis patients with and without treatment to levels in healthy people in Iraq. Materials and Methods: The study included 310 subjects, males and females aged (25-65) years. The patients were attending a dermatology consultant at Al-Yarmouk Teaching Hospital in Baghdad. Blood samples were collected by venipuncture from all individuals. The Sandwich ELISA was used to estimate serum levels of IL-2, IL-8, IL-22, TNF-alpha, IFN-gamma, ADP and Leptin. Results: Patients with psoriasis had considerably decreased lymphocyte and RBC counts while having significantly higher neutrophil, platelet, NLR, and PLR counts. WBC mean values in females and males among control groups were 7.16 ± 3.09x 103/µl and 8.6 ±3.62 x103/µl respectively. In psoriasis patients the WBC counts varied from 3.69 x103/µl to 12.8 x103/µl with a mean of 7.27 x 103/µl in female patients and from 6.47 x 103/µl to 13.62 x103/µl in males. Serum levels of cytokines, leptin and adiponectin were significantly higher in Group I patients, while in Group II it was almost like levels in the control group. Conclusion: Smoking is a risk factor for psoriasis. Lymphocytes, erythrocytes, and hemoglobin levels are decreased in patients with psoriasis, while platelets and cytokines are elevated, signifying a relationship between these immunological parameters and development and severity of psoriasis disease.

Insights into Nutritional Strategies in Psoriasis.

Psoriasis, an autoimmune chronic inflammatory skin condition, has a high incidence in the general population, reaching 2-4%. Its pathogenesis involves an interplay of genetic factors, immune disturbances, and environmental factors. Within the environmental factors that aid the appearance of this autoimmune skin disease, the Western lifestyle and overall diet play important roles in the steady growth in psoriasis prevalence. Furthermore, psoriasis is associated with comorbidities such as psoriatic arthritis, cardiovascular disease, metabolic syndrome, and obesity. Accumulating evidence suggests that obesity is an important risk factor for psoriasis. Moreover, obesity aggravates established psoriasis, and a reduction in the body mass index can improve the clinical outcomes of psoriasis and increase the efficacy of standard psoriasis therapies. The possible connection between this autoimmune disease and obesity relies on the fact that white adipose tissue is an essential endocrine organ that secretes an array of immune mediators and inflammatory and metabolic factors with pro-inflammatory action. Thus, immune-mediated mechanisms in both psoriasis and obesity conditions are common factors. This paper describes the factors that link obesity with skin autoimmune disease and highlights the importance of the stimulatory or regulatory effects of nutrients and food in psoriasis and the possible improvement of psoriasis through nutritional strategies.

Obesity-induced dysregulation of skin-resident PPARγ+ Treg cells promotes IL-17A-mediated psoriatic inflammation

Obesity is a major risk factor for psoriasis, but how obesity disrupts the regulatory mechanisms that keep skin inflammation in check is unclear. Here, we found that skin was enriched with a unique population of CD4+Foxp3+ regulatory T (Treg) cells expressing the nuclear receptor peroxisome proliferation-activated receptor gamma (PPARγ). PPARγ drove a distinctive transcriptional program and functional suppression of IL-17A+ γδ Tcell-mediated psoriatic inflammation. Diet-induced obesity, however, resulted in a reduction of PPARγ+ skin Treg cells and a corresponding loss of control over IL-17A+ γδ Tcell-mediated inflammation. Mechanistically, PPARγ+ skin Treg cells preferentially took up elevated levels of long-chain free fatty acids in obese mice, which led to cellular lipotoxicity, oxidative stress, and mitochondrial dysfunction. Harnessing the anti-inflammatory properties of these PPARγ+ skin Treg cells could have therapeutic potential for obesity-associated inflammatory skin diseases.

NARRATIVE REVIEW OF PSORIASIS: PATHOGENESIS, CLINICAL FEATURES AND MANAGEMENT STRATEGIES

Psoriasis is a chronic autoimmune disorder that affects approximately 2-3% of the global population. It is characterized by red, scaly, and itchy patches on the skin that can cause signicant discomfort and have a negative impact on patients' quality of life. Despite being a well-known condition, the pathogenesis of psoriasis remains poorly understood, and there is no cure for the disease. Therefore, the management of psoriasis primarily focuses on symptom relief and improving patients' quality of life. The epidemiology of psoriasis varies by geographic location, ethnicity, and age, with some studies suggesting a higher prevalence among certain populations. The most common subtype of psoriasis is plaque psoriasis, which is characterized by erythematous plaques covered with silvery scales. Other clinical subtypes include guttate psoriasis, pustular psoriasis, erythrodermic psoriasis, and inverse psoriasis. Each subtype has unique clinical features and requires specic management strategies. Epidemiological studies have identied several risk factors for psoriasis, including family history, smoking, obesity, and stress. The exact mechanisms by which these factors contribute to the development and progression of psoriasis are not fully understood. However, it is thought that genetic and environmental factors interact to disrupt the normal immune response and trigger the inammatory cascade that drives psoriasis pathogenesis.

The Cornified Envelope: A Versatile Contributor to the Epidermal Barrier

The Cornified Envelope: A Versatile Contributor to the Epidermal Barrier

Obesity-induced dysregulation of a unique subset of Tregs promotes skin inflammation

Abstract Obesity is associated with increased skin inflammation and is a major risk factor for psoriasis, raising the question of how obesity disrupts the regulatory mechanisms that keep skin inflammation in check at steady state. We found that skin was enriched with a unique subset of CD4 +Foxp3 +regulatory T cells (Tregs), which is critical to limit IL-17A-mediated psoriatic inflammation. Diet-induced obesity, however, resulted in a significant reduction of this subset of skin Tregs and a corresponding loss of control over IL-17A-mediated inflammation. Mechanistically, this specific skin Treg population preferentially took up elevated levels of long-chain saturated fatty acids during obesity, which led to cellular lipotoxicity and mitochondrial dysfunction. Harnessing the anti-inflammatory property of this unique subset of skin Tregs could have therapeutic potential for obesity-associated inflammatory skin diseases. Supported from grants from NIH/NIDDK (1R01DK128061), National Psoriasis Foundation, and Emory University Research Committee (URC).

Periodontal disease does not increase the risk of subsequent psoriasis

Previous studies suggested that chronic periodontitis may be a risk factor for psoriasis. However, no study has confirmed this relationship for all stages of periodontal disease (gingivitis and periodontitis). This nationwide population-based retrospective cohort study aimed to investigate whether periodontal disease is an independent risk factor for the development of subsequent psoriasis. Patients aged ≥ 20 years who underwent both medical and oral checkups from the National Health Screening Program between 2002 and 2007 were selected from a customized database provided by the National Health Insurance Service (NHIS). Then, patients with periodontal disease (n = 3,682,468) and without periodontal disease (control, n = 3,637,128) according to oral examination results were identified. We tracked each patient for subsequent psoriasis diagnosis until the end of 2018 using NHIS database. The incidence rates of psoriasis per 1000 person-years were 0.36 and 0.34 in the periodontal disease group and control groups, respectively. After adjusting for potential cofactors, no significant increase in risk (adjusted hazard ratio, 0.994; 95% confidence interval, 0.974–1.015) was observed. Similar results were observed when analyzing the risk of psoriasis in patients who required scaling or periodontal surgery. In conclusion, periodontal disease is not an independent risk factor of psoriasis.

Smoking is an independent but not a causal risk factor for moderate to severe psoriasis: A Mendelian randomization study of 105,912 individuals.

Smoking is strongly associated with higher risk of psoriasis in several observational studies; however, whether this association is causal or can be explained by confounding or reverse causation is not fully understood. Randomized controlled trials are the gold standard when examining causality; however, when this method is not feasible, the Mendelian randomization design is an alternative. Herein genetic variants can be used as robust proxies for modifiable exposures and thereby avoiding confounding and reverse causation.In this study, we hypothesized that smoking is an independent and causal risk factor for psoriasis and tested this using a Mendelian randomization design. We used data from the Copenhagen General Population Study including 105,912 individuals with full information on lifestyle factors, biochemistry, and genotype data. In total, 1,240 cases of moderate to severe psoriasis were included to investigate the association between smoking and psoriasis. To assess causality of the association, we used the genetic variant CHRNA3 rs1051730, where the T-allele is strongly associated with high lifelong cumulative smoking, as a proxy for smoking. In observational analyses, the multivariable adjusted hazard ratio of developing moderate to severe psoriasis was 1.64 (95% confidence interval: 1.35-2.00) in ever smokers with ≤ 20 pack-years and 2.23 (1.82-2.73) in ever smokers with > 20 pack-years compared to never smokers. In genetic analyses, the odds ratio of developing moderate to severe psoriasis was 1.05 (0.95-1.16) per CHRNA3 rs10511730 T-allele in ever smokers. Smoking was an independent risk factor for moderate to severe psoriasis in observational analyses. However, using a genetic variant as a robust proxy for smoking, we did not find this association to be causal.

CYSRT1: An Antimicrobial Epidermal Protein that Can Interact with Late Cornified Envelope Proteins

Late cornified envelope (LCE) proteins are small cationic epidermal proteins with antimicrobial properties, and the combined deletion of LCE3B and LCE3C genes is a risk factor for psoriasis that affects skin microbiome composition. In a yeast two-hybrid screen, we identified CYSRT1 as an interacting partner of members of all LCE groups except LCE6. These interactions were confirmed in a mammalian cell system by coimmunoprecipitation. CYSRT1 is a protein of unknown function that is specifically expressed in cutaneous and oral epithelia and spatially colocalizes with LCE proteins in the upper layers of the suprabasal epidermis. Constitutive CYSRT1 expression is present in fully differentiated epidermis and can be further induced invivo by disruption of the skin barrier upon stratum corneum removal. Transcriptional regulation correlates to keratinocyte terminal differentiation but not to skin bacteria exposure. Similar to LCEs, CYSRT1 was found to have antibacterial activity against Pseudomonas aeruginosa. Comparative gene sequence analysis and protein amino acid alignment indicate that CYSRT1 is highly conserved among vertebrates and has putative antimicrobial activity. To summarize, we identified CYSRT1 in the outer skin layer, where it colocalizes with LCE proteins and contributes to the constitutive epidermal antimicrobial host defense repertoire.