11 research outputs found

    Leptin Receptor (rs1137101) and Brain-Derived Neurotrophic Factor (rs925946) Gene Variants Are Associated with Obesity in the Early- but Not in the Late-Onset Population of Hungarian Psoriatic Patients

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    Background: Psoriatic patients have considerably higher odds of being obese compared with the general population; however, the exact pathophysiological link between psoriasis and obesity needs to be elucidated. Methods: To investigate the association of psoriasis with established obesity-related gene variants, we conducted a population-based case-control study including 3541 subjects (574 psoriasis cases and 2967 controls from the general Hungarian population). Genotyping of 20 SNPs at ADIPOQ, BDNF, FTO, GNPDA2, LEPR, MC4R, NEGR1, NPY, PPARG, TMEM18, and UCP2 were determined, and differences in genotype and allele distributions were investigated. Multiple logistic regression analyses were implemented. Results: Analysis revealed an association between the G allele of the rs1137101 polymorphism (LEPR gene) and obesity risk (OR: 3.30 (1.45; 7.50), p = 0.004) in the early-onset group of psoriatic patients. Furthermore, the T allele of rs925946 polymorphism (BDNF gene) was also associated with increased risk of obesity in early-onset psoriasis (OR: 2.26 (1.24; 4.14), p = 0.008). Conclusions: Our results suggest that in psoriatic patients, there are prominent differences in the causes of obesity that should be accounted for, including not only environmental factors but also patient characteristics, such as the time of disease onset as well as genetic factors

    TLR1/2 and TLR4 pathways induce similar changes in the gene expression profile of SZ95 sebocytes.

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    <p>(A)Venn diagram visualizing genes that are regulated both by PAM3CSK4 and LPS in SZ95 sebocytes at 6 (orange) and 24 hours (dark blue). Note the large number of genes that are regulated by both stimuli at 6 hours and an even greater number at 24 hours. (B) Differentially expressed genes in untreated, LPS or PAM3CSK4 treated SZ95 sebocytes at 6 and 24 hours as observed by our RNAseq analysis shown as a heat map. Color intensities reflect the ratios of signal intensities as shown. Note that the detected changes were due to a sustained up-regulation in the vast majority of genes, while no genes with a significant down-regulation at both time-points were detected.</p

    Identifying Serum amyloid A 1/2 as a marker for inflamed sebocytes.

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    <p>(A)Venn diagram visualizing the number of genes showing significantly different expression levels between treatment conditions (LPS and PAM3CSK4 treated SZ95 sebocytes at 6 and 24 hours when compared to untreated SZ95 sebocytes) as observed by our RNAseq analysis. Note that 207 genes were identified as differentially regulated in any of the examined conditions and time points, marked by yellow. (B) Venn diagram visualizing the overlap of the 207 genes and the differentially regulated genes in acne samples from available gene expression profiles (2). Note that 56 out of the 207 genes were significantly regulated also in acne samples. (C) Hierarchical clustering of the 56 genes that are differentially expressed in any of the conditions of LPS and PAM3CSK4 treated SZ95 sebocytes when compared to untreated cells both at 6 and at 24 hours and are also significantly altered in acne samples when compared to control ones as observed in the gene expression profiles of acne samples from the available work of Kelhala HL et al. (NCBI GEO accession number: GSE5379) (2). Out of the 56 genes presented on the heat map, Serum amyloid A 1/2 is highlighted, fulfilling our criteria (up-regulated in acne samples as well as by both treatments, its expression levels increased from 6 to 24 hours, detectable also at the level of protein) to define a possible marker for inflamed sebocytes. (D) Western blot analysis of SAA1/2 in control, LPS and PAM3CSK4 treated SZ95 sebocytes 24 h after treatment.</p

    Meta-analysis using gene expression profiles from acne samples, TLR1/2- and TLR4-activated SZ95 sebocytes reveals a possible contribution of sebocytes to the inflammatory environment in acne.

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    <p>(A) Genes significantly up-regulated in acne samples (red circle) when compared to control samples and genes up-regulated in LPS (green circle) or PAM3CSK4 (blue circles) treated SZ95 sebocytes when compared to untreated cells at 24 hours are visualized as a Venn diagram. Gene expression data of acne samples were obtained from available gene expression profiles (2). (B) Overlapping genes presented in a heat map were functionally categorized using the Cytoscape classification system. (C) Biological process analysis by Cytoscape Analysis confirmed that sebocytes are possible candidates for contributing to the inflammatory environment in acne samples.</p

    Clustering of the altered genes in response to TLR1/2 or TLR4 activation in SZ95 sebocytes.

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    <p>Genes that were regulated both by PAM3CSK4 and LPS were functionally categorized using the Cytoscape classification system. The clusters clearly defined an immunocompetence for the activated sebocytes and pointed on so far unrevealed functions such as a possible involvement in wounding and leukocyte migration. Note that in black are the genes/clusters present in both the early (6 hours) as well as in the late responder (24 hours) group, while the genes in bold falling to the functional category of cholesterol metabolic process were only detected at 24 hours.</p
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