Browsing by Author "Román, Manuel"

Introduction: Epigenetic factors play an important role in psoriasis onset and development. Biological drugs are used to treat moderate-to-severe psoriasis patients resistant to conventional systemic drugs. Although they are safe and effective, some patients do not respond to them. Therefore, it is necessary to find biomarkers that could predict response to these therapies. Objective: To find epigenetic biomarkers that could predict response to biological drugs (ustekinumab, secukinumab, adalimumab, ixekizumab). Materials and methods: Peripheral blood mononuclear cells (PBMCs) were isolated from 39 psoriasis patients treated with biological therapies before and after drug administration and from 42 healthy subjects. Afterwards, histones were extracted from PBMCs. Four histone modifications (H3 and H4 acetylation, H3K4 and H3K27 methylation) were determined by ELISA. Data were analysed by IBM-SPSS v.23. Results and conclusions: Psoriasis patients presented reduced levels of acetylated H3 and H4 and increased levels of methylated H3K4 compared to controls. Non-significant changes were observed after treatment administration in any of the histone modifications analysed. Nevertheless, significant changes in methylated H3K27 were found between responders and non-responders to biological drugs at 3 months. As 28% of these patients also presented psoriatic arthritis (PsA), the former analysis was repeated in the subsets of patients with or without PsA. In patients without PsA, significant changes in methylated H3K4 were found between responders and non-responders to biological drugs at 3 and 6 months. Although further studies should confirm these results, these findings suggest that H3K27 and H3K4 methylation may contribute to patients’ response to biological drugs in psoriasis.

Aim: The aim was to evaluate the effect of polymorphisms in metabolizing enzymes and transporters on the pharmacokinetics, pharmacodynamics and adverse effects of trazodone in healthy volunteers. Materials & methods: 36 healthy volunteers receiving a single 100-mg oral dose of trazodone were genotyped for 11 variants in CYP3A4, CYP3A5, CYP2D6 and ABCB1 by real-time PCR. Plasma concentrations were measured using liquid chromatography-tandem mass spectrometry method. Results & conclusion: Sex affected the pharmacokinetics of trazodone with higher clearance in women. Polymorphisms in ABCB1, but not in CYP3A or CYP2D6, influenced trazodone pharmacokinetics. Trazodone decreased blood pressure and prolonged the corrected QT interval interval. CYP2D6 and ABCB1 polymorphisms were associated with the incidence of dizziness and prolonged corrected QT interval, respectively. Subjects with adverse drug reactions had lower concentrations of trazodone suggesting its metabolite (m-chlorophenylpiperazine) could be responsible for these effects.

Aims-. This study evaluated the influence of pharmacogenetics in psoriatic patients treated with adalimumab and/or infliximab. Materials and methods-. Prospective observational study evaluating the association of 124 polymorphisms with the response to adalimumab or infliximab (PASI75) in patients with moderate-to-severe plaque psoriasis at 3 months (N=95) and 6 months of treatment (N=90). Significant SNPs for univariate analysis were subjected to multivariate analysis. Results/Conclusions-. Five SNPs were associated with PASI75 at 3 months: rs6661932 (IVL), rs2546890 (IL12B), rs2145623 (NFKBIA), rs9304742 (ZNF816A) and rs645544 (SLC9A8). Furthermore, rs1061624 (TNFR1B) was associated with PASI75 at 6 months. Nevertheless, these biomarkers should be validated in large-scale studies before implementation in clinical practice.