Dataset Information

TaaI/Cdx-2 AA Variant of VDR Defines the Response to Phototherapy amongst Patients with Psoriasis.

ABSTRACT: 1,25-dihydroxyvitamin-D₃ plays a central role in the immune system via binding to the vitamin D receptor. VDR polymorphisms have been associated with multiple autoimmune disorders, including psoriasis. Until now, five VDR polymorphisms, FokI, ApaI, BsmI, TaqI and TaaI/Cdx2, have been studied in psoriasis, with contradicting results. Therefore, this study aimed to evaluate the association of VDR polymorphisms with susceptibility to psoriasis, effectiveness of NB-UVB phototherapy and concentration of proinflammatory cytokines and vitamin D amongst the Polish population. VDR polymorphisms were analyzed by PCR-RFLP or real-time PCR. We found that the frequency of the TaaI/Cdx-2 GG genotype was significantly higher in psoriasis patients and was associated with regulation of IL-17 and IL-23 concentration. Moreover, TaaI/Cdx-2 AA might have a significant effect on the response to phototherapy amongst patients with psoriasis. Our results suggest that VDR is a susceptibility factor for psoriasis development. Moreover, TaaI/Cdx-2 variants have a significant effect on the response to phototherapy amongst patients with psoriasis and regulation of inflammatory response via decrease of IL-17 and IL-23 level after UVB phototherapy in the Polish population. Results of our study provide some evidence in support of the hypothesis that the vitamin D signaling pathway may be of relevance for pathogenesis and treatment of psoriasis.

SUBMITTER: Lesiak A

PROVIDER: S-EPMC8234577 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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TaaI/Cdx-2 AA Variant of VDR Defines the Response to Phototherapy amongst Patients with Psoriasis.

Lesiak Aleksandra A Wódz Karolina K Ciążyńska Magdalena M Skibinska Małgorzata M Waszczykowski Michał M Ciążyński Karol K Olejniczak-Staruch Irmina I Sobolewska-Sztychny Dorota D Narbutt Joanna J

Life (Basel, Switzerland) 20210616 6

1,25-dihydroxyvitamin-D3 plays a central role in the immune system via binding to the vitamin D receptor. VDR polymorphisms have been associated with multiple autoimmune disorders, including psoriasis. Until now, five VDR polymorphisms, FokI, ApaI, BsmI, TaqI and TaaI/Cdx2, have been studied in psoriasis, with contradicting results. Therefore, this study aimed to evaluate the association of VDR polymorphisms with susceptibility t ...[more]

PMID: 34208603

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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.

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.

Dataset Information

TaaI/Cdx-2 AA Variant of VDR Defines the Response to Phototherapy amongst Patients with Psoriasis.

Publications

<i>TaaI</i>/Cdx-2 AA Variant of <i>VDR</i> Defines the Response to Phototherapy amongst Patients with Psoriasis.

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