Reduced Psoriasis Risk Research Articles

Association of Lipid-Lowering Drugs With Risk of Psoriasis

Lipid pathways have been implicated in the pathogenesis of psoriasis, and some lipid-lowering drugs, such as statins, are hypothesized to have disease-modifying properties. However, large population-level studies are scarce, and causal interpretation of results from traditional observational designs is limited by confounding. To investigate the causal association between genetically proxied lipid-lowering drugs and psoriasis risk. This 2-sample mendelian randomization study was performed from August to October 2022 and included population-level genome-wide association studies of psoriasis in the UK Biobank and FinnGen studies and low-density lipoprotein (LDL) by the Global Lipids Genetics Consortium. The inverse variance-weighted method was used with pleiotropy robust methods and colocalization as sensitivity analyses. Genetically proxied inhibition of 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR, targeted by statins), Niemann-Pick C1-like 1 (NPC1L1, targeted by ezetimibe), and proprotein convertase subtilisin/kexin type 9 (PCSK9, targeted by, eg, alirocumab), using LDL as the biomarker. Risk of psoriasis. Data from 12 116 patients with psoriasis and approximately 1.3 million individuals with LDL measurement were analyzed. Genetically proxied PCSK9 inhibition was associated with reduced risk of psoriasis (odds ratio, 0.69 per standard deviation reduction in LDL; 95% CI, 0.55-0.88; P = .003), which was replicated in FinnGen (odds ratio, 0.71; 95% CI, 0.57-0.88; P = .002). Sensitivity analyses did not provide statistical evidence of bias from pleiotropy or genetic confounding. No robust association was found for HMGCR or NPC1L1 inhibition. This mendelian randomization study suggests that PCSK9 is implicated in psoriasis pathogenesis, and its inhibition is associated with reduced psoriasis risk. These findings potentially pave the way for future studies that may allow personalized selection of lipid-lowering drugs for those at risk of psoriasis.

Tumor Necrosis Factor-α 308 G/A polymorphism and psoriasis risk: A pooled analysis in different populations.

More and more researches have been carried out on the association between the tumor necrosis factor-α (TNF-α) 308 G/A polymorphism and psoriasis, however, controversial results have emerged in these studies. This meta-analysis was performed to quantitatively clarify the relationship between TNF-α 308 G/A polymorphism and the risk of psoriasis in different populations. Databases of PubMed, Springer Link, Ovid, Chinese Wanfang Data Bases, Chinese National Knowledge Infrastructure and Chinese Biology Medicine were investigated until June 2019. The association between the TNF-α 308 G/A polymorphism and psoriasis was evaluated by calculating the pooled odds ratio (OR) and 95% confidence intervals (CIs). A total of 26 studies including 3657 patients and 3197 controls were screened out. In the overall population, the pooled results showed a reduced psoriasis risk with the TNF-α 308 G/A polymorphism (A vs G: OR = 0.77, 95% CI = 0.67-0.89; AA+GA vs GG: OR = 0.72, 95% CI = 0.61–0.86). In the subgroup analysis stratified by geographic locations, the TNF-α 308 G/A polymorphism was significantly associated with a reduced risk of psoriasis in Germany (A vs G: OR = 0.67, 95% CI = 0.57–0.78; AA+GA vs GG: OR = 0.62, 95% CI = 0.52–0.75), as well as in China (AA+GA vs GG: OR = 0.71, 95% CI = 0.52–0.98) and Poland (A vs G: OR = 0.61, 95% CI = 0.38–0.97; AA+GA vs GG: OR = 0.59, 95% CI = 0.35–0.99). This study indicated a significantly reduced psoriasis risk associated with the TNF-α 308 G/A polymorphism in Germans, as well as in Chinese and Poles populations compared with other populations. Ethnicity and geographic locations probably play a pivotal role in the genetic association of psoriasis.

Association of the tumour necrosis factor-α polymorphisms rs361525 and rs1800629 with susceptibility to psoriasis: a meta-analysis

Evidence has suggested that tumour necrosis factor (TNF)-α may be involved in the aetiology of psoriasis, but the underlying association of the TNF-α polymorphisms -238G/A (rs361525) and -308G/A (rs1800629) with the risk of psoriasis is still unconfirmed. This meta-analysis was performed to determine whether the TNF-α -238G/A and -308G/A polymorphisms are associated with susceptibility to psoriasis. Eligible studies were identified by searching PubMed, EMBASE, CNKI (China National Knowledge Infrastructure), CBM (Chinese biomedical literature database) and WANFANG databases within a range of published years from 1990 to August 2012. The odds ratio (OR) and 95% confidence interval (CI) were used to assess the different associations. In total, 17 studies with 2847 cases and 2222 controls were found for -238G/A and 20 studies with 2975 cases and 2243 controls for -308G/A. The pooled results showed an overall increased risk of psoriasis for the -238G/A polymorphism (OR = 2.06, 95% CI = 1.45-2.94, P < 0.001 for AA/GA vs. GG) and a reduced psoriasis risk with the -308G/A polymorphism (OR = 0.68, 95% CI = 0.59-0.79, P < 0.001 for AA/GA vs. GG). This association was only present in early-onset psoriasis (OR = 3.68, 95% CI = 2.17-6.24, P < 0.001 for -238G/A; OR = 0.56, 95% CI = 0.43-0.72, P < 0.001 for -308G/A), whereas there was no association (OR = 0.98, 95% CI = 0.56-1.70, P = 0.92 for -238G/A) or a unreliable association (OR = 0.66, 95% CI = 0.46-0.94, P = 0.02 for -308G/A) in late-onset psoriasis. This meta-analysis suggests that the TNF-α -238 and -308 promoter polymorphisms may play different roles in conferring susceptibility to psoriasis. Functional and well-designed studies should be conducted to confirm these results.

Statin use and risk of first-time psoriasis diagnosis

Statins have been suggested as a potential treatment for psoriasis because of their anti-inflammatory properties. However, evidence on the benefits of statins is scarce. We sought to study the association between use of statins or other lipid-lowering agents and the risk of developing psoriasis. We conducted a case-control analysis using the United Kingdom-based General Practice Research Database. We identified patients with an incident psoriasis diagnosis between 1994 and 2005 and matched one control subject to each patient on age, sex, general practice, calendar time, and years of history in the database. We estimated odds ratios (ORs) with 95% confidence intervals (CIs), stratified exposure by timing and duration, and adjusted the ORs for potential confounders. We identified 36,702 incident psoriasis cases and the same number of matched controls. Adjusted ORs for current use (last prescription <30 days before index date) of 1 to 4, 5 to 19, or greater than or equal to 20 prescriptions for statins, as compared with nonuse, were 0.60 (95% CI 0.45-0.80), 1.00 (95% CI 0.84-1.18), and 1.08 (95% CI 0.92-1.28), respectively. The ORs for recent and past use (last prescription 30-89 days and ≥90 days ago, respectively) were around 1, except for past use of 1 to 4 prescriptions (OR 1.39; 95% CI 1.09-1.78). Potential of residual confounding as a result of retrospective study design is a limitation. This large case-control study does not provide evidence for an altered risk of developing psoriasis in association with long-term use of statins. The reduced psoriasis risk for current short-term statin users is interesting, but whether the association is indeed causal needs further investigation.

Lithium, Antipsychotics, and Risk of Psoriasis

Observations in controlled trials and case reports have linked lithium exposure to induction or exacerbation of psoriasis. A causal relationship between lithium exposure and incident psoriasis has been questioned, and observational studies are lacking. We conducted a case-control analysis using the United Kingdom-based General Practice Research Database to study the association between the use of lithium or antipsychotics and the risk of developing an incident diagnosis of psoriasis. We identified cases with an incident diagnosis of psoriasis between 1994 and 2005, and controls were matched to the cases on age, sex, general practice, calendar time, and years of history in the database. We used conditional logistic regression to estimate the risk of developing a first-time diagnosis of psoriasis in relation to previous exposure to lithium and antipsychotic drugs, stratified by exposure timing and duration. We calculated odds ratios (ORs) with 95% confidence intervals (CIs) adjusted for smoking, body mass index, and additional potential confounders. We identified 36,702 incident cases of psoriasis and the same number of matched controls. Compared with nonuse, current use of 5 or more prescriptions for lithium and atypical antipsychotics yielded adjusted ORs of 1.68 (95% CI, 1.18-2.39; P < 0.01) and 0.76 (95% CI, 0.55-1.06; P = 0.11), respectively. The OR for olanzapine was 0.50 (95% CI, 0.28-0.89, P = 0.02). Long-term use of lithium was associated with a small increase in risk of incident psoriasis. There was a suggestion of a possible reduced psoriasis risk associated with the use of atypical antipsychotics, mainly olanzapine, a finding that needs further evaluation.

Association between use of thiazolidinediones or other oral antidiabetics and psoriasis: A population based case-control study

Small clinical trials suggest that thiazolidinediones may exert a beneficial effect on skin lesions of patients with psoriasis. Little is known about other classes of antidiabetic drugs and the psoriasis risk. We sought to study the association between use of thiazolidinediones, sulfonylureas, biguanides, or acarbose and the risk of developing a first-time diagnosis of psoriasis. We conducted a case-control analysis on the United Kingdom-based General Practice Research Database. We identified patients with an incident psoriasis diagnosis from 1994 to 2005 and matched one control subject to each patient on age, sex, general practice, calendar time, and years of history in the database. Conditional logistic regression was used to estimate the odds ratio with 95% confidence intervals (CI) of developing a first-time psoriasis diagnosis in relation to previous exposure to antidiabetic drugs, stratified by exposure timing and duration of use and adjusted for a variety of potential confounders. We identified 36,702 patients with a first-time psoriasis diagnosis and the same number of matched control subjects. As compared with no use, the adjusted odds ratio for current use of 1 to 4 prescriptions or greater than or equal to 5 prescriptions for thiazolidinediones were 1.01 (95% CI 0.34-3.01) and 0.33 (95% CI 0.16-0.66), respectively. Current use of greater than or equal to 15 prescriptions for metformin or sulfonylureas yielded adjusted odds ratio of 0.77 (95% CI 0.62-0.96) and 1.07 (95% CI 0.88-1.31), respectively. The findings are based on a small number of patients exposed to thiazolidinediones (100 in total, 48 current users of >or=5 prescriptions). The findings of this large observational study provide further evidence for a potentially beneficial effect of thiazolidinediones on psoriasis. While current long-term use of metformin was also associated with a suggestion of a reduced psoriasis risk, no such effect was seen for use of other oral antidiabetics.

TNF-α Gene Promoter -238G>A and -308G>A Polymorphisms Alter Risk of Psoriasis Vulgaris: A Meta-Analysis

Tumor necrosis factor-alpha (TNF-alpha) is a major proinflammatory cytokine and involved in the etiology of psoriasis. The -238G>A and -308G>A polymorphisms influence the transcription of the TNF-alpha gene and have been implicated in psoriasis risk. However, the results from the published studies on the association between TNF-alpha polymorphisms and psoriasis risk are conflicting. Our meta-analysis of a total of 997 psoriasis cases and 943 control subjects from eight published case-control studies for the -238G>A polymorphism and of 1,156 psoriasis cases and 1,083 control subjects from 10 published case-control studies for the -308G>A polymorphism showed that a significantly increased risk was associated with the variant GA+AA genotypes of -238G>A, compared with the GG genotype (odds ratio (OR) 2.60, 95% confidence interval (95% CI) 1.48-4.56), whereas a significantly reduced psoriasis risk was associated with the variant GA+AA genotypes of the -308G>A compared with the GG genotype (OR 0.57, 95% CI 0.45-0.71). Our findings suggest that TNF-alpha -238G>A and -308G>A polymorphisms might be used as biomarkers for psoriasis risk prediction. A single larger study with thousands of subjects and biochemical and biological characterization is warranted to evaluate further the role of -238G>A and -308G>A polymorphisms and psoriasis risk in a population of various ethnicities.