Significance of Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) for the Monitoring of Treatment Response to Cyclosporine in Patients with Psoriasis

Frątczak, Aleksandra; Miziołek, Bartosz; Łupicka-Słowik, Agnieszka; Sieńczyk, Marcin; Polak, Karina; Bergler-Czop, Beata

doi:10.3390/life13091873

Cited by 2 publications

(1 citation statement)

References 28 publications

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“…Its significance as a pivotal therapeutic target for hypercholesterolemia and coronary heart disease attenuation is evident [ 26 ]. A clinical study showed that the levels of PCSK9 in serum were moderately to severely correlated with the levels of LDL and total cholesterol (TChol) [ 27 ]. The FOURIER study demonstrated that PCSK9 inhibitors profoundly expunge LDL cholesterol from the circulatory system, leading to attenuated cardiovascular adversities [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Genetically proxied PCSK9 inhibition is associated with reduced psoriatic arthritis risk

Li,

Lin

et al. 2024

Inflamm. Res.

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Background Lipid pathways play a crucial role in psoriatic arthritis development, and some lipid-lowering drugs are believed to have therapeutic benefits due to their anti-inflammatory properties. Traditional observational studies face issues with confounding factors, complicating the interpretation of causality. This study seeks to determine the genetic link between these medications and the risk of psoriatic arthritis. Methods This drug target study utilized the Mendelian randomization strategy. We harnessed high-quality data from population-level genome-wide association studies sourced from the UK Biobank and FinnGen databases. The inverse variance-weighted method, complemented by robust pleiotropy methods, was employed. We examined the causal relationships between three lipid-lowering agents and psoriatic arthritis to unveil the underlying mechanisms. Results A significant association was observed between genetically represented proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition and a decreased risk of psoriatic arthritis (odds ratio [OR]: 0.51; 95% CI 0.14–0.88; P < 0.01). This association was further corroborated in an independent dataset (OR 0.60; 95% CI 0.25–0.94; P = 0.03). Sensitivity analyses affirmed the absence of statistical evidence for pleiotropic or genetic confounding biases. However, no substantial associations were identified for either 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors or Niemann–Pick C1-like 1 inhibitors. Conclusions This Mendelian randomization analysis underscores the pivotal role of PCSK9 in the etiology of psoriatic arthritis. Inhibition of PCSK9 is associated with reduced psoriatic arthritis risk, highlighting the potential therapeutic benefits of existing PCSK9 inhibitors.

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Section: Discussionmentioning

confidence: 99%

Genetically proxied PCSK9 inhibition is associated with reduced psoriatic arthritis risk

Li,

Lin

et al. 2024

Inflamm. Res.

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Causal effects of lipid-lowering drugs on skin diseases: a two-sample Mendelian randomization study

Liu,

Bian

2024

Front. Med.

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BackgroundAlthough previous studies have indicated an association between low-density lipoprotein (LDL) and skin diseases, their causal effects remain inconclusive. This study aimed to assess the causal relationship between genetically proxied lipid-lowering drugs and skin cancers and psoriasis.MethodsTwo-sample Mendelian randomization (MR) analysis was performed using single-nucleotide polymorphisms (SNPs) from genome-wide association studies (GWAS). The inverse-variance weighted (IVW) method was used to determine causal relationships. The “leave-one-out” sensitivity test, Cochran’s Q-statistic and MR-Egger intercept were used to assess heterogeneity and horizontal pleiotropy.ResultsWe identified 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and proprotein convertase subtilisin-kexin type 9 (PCSK9) as genetically proxied lipid-lowering drugs. Genetically proxied inhibition of HMGCR (stains) was causally associated with reduced risk of nonmelanoma skin cancer (OR 0.982, 95% CI 0.967–0.997, p = 0.016 by weighted median; OR 0.977, 95% CI 0.966–0.989, p < 0.001 by IVW) and psoriasis (OR 0.585, 95% CI 0.378–0.905, p = 0.016 by IVW), while PCSK9 inhibition (alirocumab) was causally associated with reduced risk of psoriasis (OR 0.560, 95% CI 0.413–0.761 by weighted median; OR 0.564, 95% CI 0.447–0.712 by IVW; p < 0.001) in the ieu-b-5089 dataset. Similar results were observed in the ieu-b-110 dataset for HMGCR and PCSK9. Sensitivity analysis revealed no evidence of heterogeneity or horizontal pleiotropy.ConclusionThis study revealed the existing HMGCR inhibitors (stains) might be protective for reducing nonmelanoma skin cancer risk, and HMGCR inhibitors (stains) and PCSK9 inhibitor (alirocumab) might be promising for reducing psoriasis risk in the European population.

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Significance of Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) for the Monitoring of Treatment Response to Cyclosporine in Patients with Psoriasis

Cited by 2 publications

References 28 publications

Genetically proxied PCSK9 inhibition is associated with reduced psoriatic arthritis risk

Genetically proxied PCSK9 inhibition is associated with reduced psoriatic arthritis risk

Causal effects of lipid-lowering drugs on skin diseases: a two-sample Mendelian randomization study

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