TaaI/Cdx-2 AA Variant of VDR Defines the Response to Phototherapy amongst Patients with Psoriasis.
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ABSTRACT:
SUBMITTER: Lesiak A
PROVIDER: S-EPMC8234577 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:A retrospective study of 200 psoriasis patients and 100 healthy donors in a Spanish cohort was carried out to study the comorbidities associated with psoriasis and their association with the response to phototherapy. The results showed a higher incidence of psychiatric disease, liver disease, kidney disease, hypertension, heart disease, vascular disease, diabetes, gastrointestinal disease, autoimmune and infectious diseases, dyslipidemia, and psoriatic arthritis in patients with psoriasis than in the control group. The incidence of comorbidities was higher in psoriasis patients over 40 years old than in the control individuals of the same age, which could be indicative of premature aging. Phototherapy was seen to be an effective treatment in cases of moderate-severe psoriasis, total whitening being achieved in more than 30% of patients, with women showing a better response than men. Narrow-band ultraviolet B was found to be the most effective type of phototherapy, although achievement of PASI100 was lower in patients with liver disease, hypertension, heart disease, vascular disease, or diabetes. Strikingly, liver disease and anemia comorbidities favored therapeutic failure. Finally, zebrafish and human 3D organotypic models of psoriasis point to the therapeutic benefit of inhibiting the glucose transporter GLUT1 and the major regulator of blood glucose dipeptidyl peptidase 4. Our study reveals that specific comorbidities of psoriasis patients are associated to failure of phototherapy and, therefore, need to be considered when planning treatment for these patients.
| S-EPMC9455671 | biostudies-literature
Project description:IntroductionVitamin D (VD) levels were correlated with different health conditions, including reproductive disorders in males. Vitamin D action is mediated through vitamin D receptor (VDR), which acts as a transcription factor. VDR gene promoter is embedded in a GC-rich island. The VDR gene has been shown to have several polymorphisms that affect the receptor function.AimTo examine the relationship between Cdx-2 polymorphism (rs17883968), the methylation status of VDR's promoter and serum levels of 25-hydroxyvitamin D in male infertility.Patients and methodsA total of 69 infertile men and 37 age-matched controls were enrolled in this study. Vitamin D level assessments were detected using the electrochemiluminescent method. Cdx-2 VDR polymorphism identification was performed by PCR on DNA samples from blood, followed by restriction. Methylation of VDR gene promoter was assessed by qMS-PCR using bisulfite-treated DNA from fresh sperm.ResultsVitamin D levels was found to be significantly decreased in infertile groups compared the controls (p=0.0279). The GG genotype was found in a higher percentage in controls and the AA genotype was higher in infertile group (p=0.0056). Infertile homozygote (GG) and heterozygote (GA) individuals had significantly higher vitamin D levels than AA homozygote. Methylation is higher in individuals with lower vitamin D levels and AA genotype is characterized by higher methylation values.ConclusionThe results provide new insights of Cdx-2 polymorphism is involved in vitamin D deficiency, highlighting the important role of epigenetic modification of vitamin D receptor and male infertility along with the genetic context.
| S-EPMC6516584 | biostudies-literature
Project description:Psoriasis is a common chronic inflammatory and hyperproliferative immune-mediated skin disorder. Narrow-band UVB (NB-UVB) phototherapy is a convenient first-line treatment of psoriasis, though the mechanisms underlying its efficacy have not been completely elucidated. In order to improve our understanding of NB-UVB phototherapy, gene expression profiling was used to characterize gene expression in lesional epidermis from psoriasis patients undergoing NB-UVB phototherapy. Increased expression of melanogenesis pathway genes was observed to be the earliest response. At the end of treatment, genes involved in diverse biological processes were affected, such as pigmentation, cell adhesion, ectodermal development and metabolism. The relationship between gene expression and treatment outcome was further studied using Partial Least Squares Discriminant Analysis (PLS-DA). Gene ontology analysis showed that genes responding to phototherapy and highly correlated to treatment outcome were involved in oxidation reduction, growth and mitochondria organization. In particular SPATA18, a key regulator of mitochondria quality, was found to be significantly downregulated in psoriasis, and its upregulation following phototherapy was required for optimal clinical improvement. Our data suggest that oxidation reduction is a critical event for the resolution of psoriatic plaques. Twelve patients diagnosed with plaque type psoriasis were recruited to the study. NB-UVB irradiation was administered to the whole body two to three times a week. Treatment comprising approximately 24 sessions was given during two to three months. A total of six 4 mm diameter punch biopsies were taken from lesions on each psoriasis patient: two prior to UV treatment (pre-UV), two at the middle stage of UV treatment (after about one month of treatment, mid-UV) and two before the last treatment session (post-UV). Twelve healthy age-, sex- and skin type-matched volunteers were also recruited and two punch biopsies were taken from the buttocks. RNA was extracted from Laser capture microdissected epidermis.
2013-12-23 | E-GEOD-53431 | biostudies-arrayexpress
Project description:Psoriasis is a common chronic inflammatory and hyperproliferative immune-mediated skin disorder. Narrow-band UVB (NB-UVB) phototherapy is a convenient first-line treatment of psoriasis, though the mechanisms underlying its efficacy have not been completely elucidated. In order to improve our understanding of NB-UVB phototherapy, gene expression profiling was used to characterize gene expression in lesional epidermis from psoriasis patients undergoing NB-UVB phototherapy. Increased expression of melanogenesis pathway genes was observed to be the earliest response. At the end of treatment, genes involved in diverse biological processes were affected, such as pigmentation, cell adhesion, ectodermal development and metabolism. The relationship between gene expression and treatment outcome was further studied using Partial Least Squares Discriminant Analysis (PLS-DA). Gene ontology analysis showed that genes responding to phototherapy and highly correlated to treatment outcome were involved in oxidation reduction, growth and mitochondria organization. In particular SPATA18, a key regulator of mitochondria quality, was found to be significantly downregulated in psoriasis, and its upregulation following phototherapy was required for optimal clinical improvement. Our data suggest that oxidation reduction is a critical event for the resolution of psoriatic plaques.
2013-12-23 | GSE53431 | GEO
Project description:Psoriasis is a major global health problem. There is a need to develop techniques to help physicians select the most appropriate cost-effective therapy for each patient. The main objectives of this study are (1) to evaluate changes in epidermal barrier function and skin homeostasis after phototherapy and (2) to explore potentially predictive values in epidermal barrier function and skin homeostasis to assess clinical improvement after fifteen sessions of phototherapy. A total of 76 subjects, 38 patients with plaque-type psoriasis and 38 gender- and age-matched healthy volunteers, were included in the study. Erythema, transepidermal water loss (TEWL), temperature, stratum corneum hydration (SCH), pH, sebum, and antioxidant capacity were measured before and after the first and fifteenth phototherapy session. Erythema (401.09 vs. 291.12 vs. 284.52 AU, p < 0.001) and TEWL (18.23 vs. 11.44 vs. 11.41 g·m-2·h-1, p < 0.001) were significantly higher at psoriatic plaques than in uninvolved psoriatic skin and healthy volunteers, respectively, while SCH was lower (9.71 vs. 44.64 vs. 40.00 AU, p < 0.001). After fifteen phototherapy sessions, TEWL (-5.19 g·m-2·h-1, p = 0.016) decreased while SCH (+7.01 AU, p = 0.013) and erythema (+30.82 AU, p = 0.083) increased at psoriatic plaques. An erythema increase exceeding 53.23 AU after the first phototherapy session, with a sensitivity of 71.4% and specificity of 84.2%, indicates that a patient may improve Psoriasis Area and Severity Index (PASI) by ≥3 points after fifteen phototherapy sessions. In conclusion, phototherapy improves epidermal barrier function in psoriatic patients and the erythema increase after one phototherapy session could help doctors select psoriasis patients who are more likely to respond to phototherapy.
| S-EPMC8432224 | biostudies-literature
Project description:BackgroundLow-dose UV treatment has been shown to be effective in mild psoriasis. However, the prolonged use of this treatment modality may raise concerns about its safety. These concerns are mainly focused on potential carcinogenic risks and overuse of this treatment modality.ObjectivesThis study was set out to evaluate possible carcinogenic risks of prolonged low-dose phototherapy.MethodsThree groups of psoriasis patients were evaluated: patients with local treatment only (n = 15); low-dose UV treatment at home for at least 18 months (n = 39); and patients with conventional NB-UVB (n = 8). Patients underwent visual inspection for signs of photoageing, and p53, CPDs and γH2AX were measured in skin biopsies. Patients undergoing low-dose phototherapy answered a survey about their recent patterns of use in a survey.ResultsIn the skin biopsies, low-dose UV treatment caused a lower amount of CPDs (p = .016) and p53 (p = .015) than NB-UVB. γH2AX did not show a significant difference. Self-report in patients undergoing low-dose phototherapy showed only one case of overuse (2.7%). Visual skin inspection showed no difference in signs of photoageing in the three groups.ConclusionProlonged treatment with low-dose UV for 18 months appears at least as safe as a course of conventional NB-UVB.
| S-EPMC9541771 | biostudies-literature
Project description: Not available
| EMPIAR-11342 | biostudies-other
Project description:Systemic AA amyloidosis is a debilitating protein misfolding disease in humans and animals. In humans, it occurs in two variants that are called 'vascular' and 'glomerular', depending on the main amyloid deposition site in the kidneys. Using cryo electron microscopy, we here show the amyloid fibril structure underlying the vascular disease variant. Fibrils purified from the tissue of such patients are mainly left-hand twisted and contain two non-equal stacks of fibril proteins. They contrast in these properties to the fibrils from the glomerular disease variant which are right-hand twisted and consist of two structurally equal stacks of fibril proteins. Our data demonstrate that the different disease variants in systemic AA amyloidosis are associated with different fibril morphologies.
| S-EPMC9700864 | biostudies-literature
Project description:ObjectiveTo assess the costs and cost effectiveness of phototherapy with ultraviolet B light provided at home compared with outpatient ultraviolet B phototherapy for psoriasis.DesignCost utility, cost effectiveness, and cost minimisation analyses performed alongside a pragmatic randomised clinical trial (the PLUTO study) at the end of phototherapy (mean 17.6 weeks) and at one year after the end of phototherapy (mean 68.4 weeks).SettingSecondary care, provided by a dermatologist in the Netherlands.Participants196 adults with psoriasis who were clinically eligible for narrowband (TL-01) ultraviolet B phototherapy were recruited from the dermatology departments of 14 hospitals and were followed until the end of phototherapy. From the end of phototherapy onwards, follow-up was continued for an unselected, consecutive group of 105 patients for one year after end of phototherapy.InterventionsUltraviolet B phototherapy provided at home (intervention) and conventional outpatient ultraviolet B phototherapy (control) in a setting reflecting routine practice in the Netherlands. Both treatments used narrowband ultraviolet B lamps (TL-01).Main outcome measuresTotal costs to society, quality adjusted life years (QALYs) as calculated using utilities measured by the EQ-5D questionnaire, and the number of days with a relevant treatment effect (>/=50% improvement of the baseline self administered psoriasis area and severity index (SAPASI)).ResultsHome phototherapy is at least as effective and safe as outpatient phototherapy, therefore allowing cost minimisation analyses (simply comparing costs). The average total costs by the end of phototherapy were euro800 for home treatment and euro752 for outpatient treatment, showing an incremental cost per patient of euro48 (95% CI euro-77 to euro174). The average total costs by one year after the end of phototherapy were euro1272 and euro1148 respectively (difference euro124, 95% CI euro-155 to euro403). Cost utility analyses revealed that patients experienced equal health benefits-that is, a gain of 0.296 versus 0.291 QALY (home v outpatient) by the end of phototherapy (difference 0.0052, -0.0244 to 0.0348) and 1.153 versus 1.126 QALY by one year after the end of phototherapy (difference 0.0267, -0.024 to 0.078). Incremental costs per QALY gained were euro9276 and euro4646 respectively, both amounts well below the normally accepted standard of euro20 000 per QALY. Cost effectiveness analyses indicated that the mean number of days with a relevant treatment effect was 42.4 versus 55.3 by the end of phototherapy (difference -12.9, -23.4 to -2.4). By one year after the end of phototherapy the number of days with a relevant treatment effect were 216.5 and 210.4 respectively (6.1, -41.1 to 53.2), yielding an incremental cost of euro20 per additional day with a relevant treatment effect.ConclusionsHome ultraviolet B phototherapy for psoriasis is not more expensive than phototherapy in an outpatient setting and proved to be cost effective. As both treatments are at least equally effective and patients express a preference for home treatment, the authors conclude that home phototherapy should be the primary treatment option for patients who are eligible for phototherapy with ultraviolet B light.Trial registrationCurrent Controlled Trials ISRCTN83025173 and Clinicaltrials.gov NCT00150930.
| S-EPMC2857750 | biostudies-literature
Project description:The cause of psoriasis, a common chronic inflammatory skin disease, is not fully understood. Microarray experiments have been widely used in recent years to identify genes associated with psoriasis pathology, by comparing expression levels of lesional (LS) with adjacent non-lesional (NL) skin. It is commonly observed that the differentially expressed genes (DEGs) differ greatly across experiments, due to variations introduced in the microarray experiment pipeline. Therefore, a statistically based meta-analytic approach, which combines the results of individual studies, is warranted. In this study, a meta-analysis was conducted on 5 microarray data sets, including 193 LS and NL pairs. We termed this the Meta-Analysis Derived (MAD) transcriptome. In "MAD-5" transcriptome, 677 genes were up-regulated and 443 were down-regulated in LS skin compared to NL skin. This represents a much larger set than the intersection of DEGs of these 5 studies, which consisted of 100 DEGs. We also analyzed 3 of the studies conducted on the Affymetrix hgu133plus2 chips and found a greater number of DEGs (1084 up- and 748 down-regulated). Top canonical pathways over-represented in the MAD transcriptome include Atherosclerosis Signaling and Fatty Acid Metabolism, while several "new" genes identified are involved in Cardiovascular Development and Lipid Metabolism. These findings highlight the relationship between psoriasis and systemic manifestations such as the metabolic syndrome and cardiovascular disease. Then, the Meta Threshold Gradient Descent Regularization (MTGDR) algorithm was used to select potential markers distinguishing LS and NL skin. The resulting set (20 genes) contained many genes that were part of the residual disease genomic profile (RDGP) or "molecular scar" after successful treatment, and also genes subject to differential methylation in LS tissues. To conclude, this MAD transcriptome yielded a reference list of reliable psoriasis DEGs, and represents a robust pool of candidates for further discovery of pathogenesis and treatment evaluation.
| S-EPMC3434204 | biostudies-literature