Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA399531 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Age related macular degeneration (AMD) is the leading cause of irreversible blindness in the elderly population worldwide. While recent studies have demonstrated strong genetic associations of single nucleotide polymorphisms within a number of genes and AMD, other modes of regulation are also likely to play a role in its aetiology. We undertook DNA methylation microarray analysis on monozygotic and dizygotic twins who were discordant for AMD and identified methylated IL17RC promoters as being present only in non-AMD control individuals rather than in AMD patients. We validated this finding of a significantly decreased level of methylation on the IL17RC promoter in AMD siblings as well as in a case control study involving 202 genetically unrelated AMD patients and 96 controls (95% CI, 0.03-0.17, P=3.1x10-8). Further, we showed that hypomethylation of the IL17RC promoter in AMD patients led to an elevated expression of its protein and mRNA in peripheral blood as well as in the retina and choroid, suggesting that the DNA methylation pattern and expression of IL17RC may potentially serve as a biomarker for the diagnosis of AMD and likely plays a role in disease pathogenesis. Affymetrix U133 plus 2.0 GeneChip was used to detect gene expression patterns of IL17RC+ and IL17RC- THP1 cells.
2012-04-30 | E-GEOD-37659 | biostudies-arrayexpress
Project description:Age-related macular degeneration (AMD) is a complex multifactorial disease with at least 34 loci contributing to genetic susceptibility. To gain functional understanding of AMD genetics, we generated DNA methylation profiles of retina from 160 individuals including both controls and cases at distinct stages of AMD. With genotypes over 8 million common single nucleotide polymorphisms (SNPs) in cis, we identified 37,453 methylation quantitative trait loci (mQTL) and by integrating transcriptome of the same samples we identified 12,505 eQTLs and 13,747 DNAm sites that affect gene expression (eQTMs). We then integrated the AMD-genome-wide association studies (GWAS) data with mQTLs and eQTLs ascertained 87 target genes that may contribute to AMD risk. Our studies expand the methylation landscape of retina and AMD leading to direct targets for biological evaluation.
2023-09-11 | GSE231536 | GEO
Project description:Age related macular degeneration (AMD) is the leading cause of irreversible blindness in the elderly population worldwide. While recent studies have demonstrated strong genetic associations of single nucleotide polymorphisms within a number of genes and AMD, other modes of regulation are also likely to play a role in its aetiology. We undertook DNA methylation microarray analysis on monozygotic and dizygotic twins who were discordant for AMD and identified methylated IL17RC promoters as being present only in non-AMD control individuals rather than in AMD patients. We validated this finding of a significantly decreased level of methylation on the IL17RC promoter in AMD siblings as well as in a case control study involving 202 genetically unrelated AMD patients and 96 controls (95% CI, 0.03-0.17, P=3.1x10-8). Further, we showed that hypomethylation of the IL17RC promoter in AMD patients led to an elevated expression of its protein and mRNA in peripheral blood as well as in the retina and choroid, suggesting that the DNA methylation pattern and expression of IL17RC may potentially serve as a biomarker for the diagnosis of AMD and likely plays a role in disease pathogenesis.
2012-05-01 | GSE37659 | GEO
Project description:Age-related macular degeneration (AMD) is a major cause of blindness in the western world. While genetic studies have linked both common and rare variants in genes involved in regulation of the complement system to increased risk of development of AMD, environmental factors, such as smoking and nutrition, can also significantly affect the risk of developing the disease and the rate of disease progression. Since epigenetics has been implicated in mediating, in part, the disease risk associated with some environmental factors, we investigated a possible epigenetic contribution to AMD. We performed genome-wide DNA methylation profiling of blood from AMD patients and controls. No differential methylation site reached genome-wide significance; however, when epigenetic changes in and around known GWASdefined AMD risk loci were explored, we found small but significant DNA methylation differences in the blood of neovascular AMD patients near age-related maculopathy susceptibility 2 (ARMS2), a top-ranked GWAS locus preferentially associated with neovascular AMD. The methylation level of one of the CpG sites significantly correlated with the genotype of the risk SNP rs10490924, suggesting a possible epigenetic mechanism of risk. Integrating genome-wide DNA methylation analysis of retina samples with and without AMD together with blood samples, we further identified a consistent, replicable change in DNA methylation in the promoter region of protease serine 50 (PRSS50). These methylation changes may identify sites in novel genes that are susceptible to non-genetic factors known to contribute to AMD development and progression.
2017-08-23 | GSE102952 | GEO
Project description:Gene methylation profiling of immortalized human mesenchymal stem cells comparing HPV E6/E7-transfected MSCs cells with human telomerase reverse transcriptase (hTERT)- and HPV E6/E7-transfected MSCs. hTERT may increase gene methylation in MSCs. Goal was to determine the effects of different transfected genes on global gene methylation in MSCs.
2011-08-25 | GSE23936 | GEO
Project description:Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly. The extent to which epigenetic changes regulate the progression of AMD is unclear. Here we profiled chromatin accessibility in the retina and retinal pigmented epithelium (RPE) from AMD patients and controls. Global decreases in chromatin accessibility occur in the RPE in early AMD and in the retina with advanced disease. Footprints of photoreceptor and RPE-specific transcription factors are enriched in differentially accessible regions (DARs) and reduced AMD. Genes associated with DARs show altered expression in AMD. Cigarette smoke, an established risk factor for AMD, applied to human iPSC-derived RPE cells recapitulates epigenomic changes seen in AMD. In addition to providing a comprehensive profile of chromatin accessibility in human RPE and retina, this study shows that global decreases in chromatin accessibility may play a critical role in AMD progression.
2018-03-05 | GSE99287 | GEO
Project description:Gene methylation profiling of immortalized human mesenchymal stem cells comparing HPV E6/E7-transfected MSCs cells with human telomerase reverse transcriptase (hTERT)- and HPV E6/E7-transfected MSCs. hTERT may increase gene methylation in MSCs. Goal was to determine the effects of different transfected genes on global gene methylation in MSCs. Two-condition experiment, KP MSCs vs. 3A6 MSCs.
2011-08-24 | E-GEOD-23936 | biostudies-arrayexpress
Project description:Background Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in the elderly population worldwide. Recent studies have demonstrated strong genetic associations between AMD and single nucleotide polymorphisms (SNPs) within genes such as CFH and HTRA1. However, we have identified monozygotic twins discordant for AMD phenotypes (one with disease, the other without disease), suggesting that an epigenetic mechanism may also contribute to the pathogenesis of AMD. Methods We identified two twin pairs with phenotypic discordance of AMD. We obtained genomic DNA from their peripheral blood mononuclear cells (PBMCs) and subjected them to DNA methylation-chip analysis (MeDIP-chip) that profiled genome-wide DNA methylation patterns on promoters of all genes and microRNAs. We next utilized the Methyl-Profiler DNA methylation assays to detect the methylation status of selected promoters. Flow cytometry and quantitative real-time PCR were used to detect the expression of the selected gene in peripheral blood cells, as well as in retinal and choroidal tissues of AMD patients and non-AMD controls. Results Our MeDIP-chip analysis identified 256 genes with hypo-methylated promoters only in the twins with AMD and 744 genes with hyper-methylated promoters only in the twins with AMD. Importantly, the promoter region of IL17RC was associated with hypo-methylated CpG sites only in the twins with AMD but not in the twins without AMD. We also found the association of the hypo-methylated IL17RC promoter with AMD in 7 pairs of siblings with discordant AMD pathology (P=0.003), as well as an independent patient cohort (95 neovascular wet and 107 geographic atrophy dry AMD patients as well as 96 non-AMD controls (95% CI, 0.01-0.10, P=9.8x10-8 for wet AMD vs. control; 95% CI, 0.05-0.32, P=2.2x10-5 for dry AMD vs. control)). Interestingly, we did not find an association between the levels of methylation on the IL17RC promoter with the previously identified genetic risk alleles in CFH, HTRA1, and ARMS2. We demonstrated an elevated expression of the IL-17RC protein in CD14+ monocytes in the peripheral blood of AMD patients as compared to non-AMD controls. These IL-17RC+ monocytes have elevated expression of CXCR1, CXCR2, and CXCR4. In addition, IL17RC was expressed only in the retinal and choroidal tissues from AMD patients but not from age-matched controls. Conclusions We show an association of the hypo-methylated IL17RC promoter with AMD, which resulted in the elevated expression of IL-17RC in peripheral blood cells as well as the retinal and choroidal tissues of AMD patients. Our study suggests that the hypo-methylated IL17RC promoter and elevated expression of IL-17RC can potentially serve as biomarkers for the diagnosis of AMD, while IL-17RC can be a new therapeutic target for AMD. In addition, our results strongly suggest an epigenetic control mechanism of AMD pathogenesis. The Affymetrix MOE430 2.0 GeneChip was used to detect gene expression patterns within the whole eye of C57B/6 normal mice.
2011-03-20 | E-GEOD-28002 | biostudies-arrayexpress
Project description:Transcriptional profiling of Homo sapiens inflammatory skin diseases (whole skin biospies): Psoriasis (Pso), vs Atopic Dermatitis (AD) vs Lichen planus (Li), vs Contact Eczema (KE), vs Healthy control (KO) In recent years, different genes and proteins have been highlighted as potential biomarkers for psoriasis, one of the most common inflammatory skin diseases worldwide. However, most of these markers are not psoriasis-specific but also found in other inflammatory disorders. We performed an unsupervised cluster analysis of gene expression profiles in 150 psoriasis patients and other inflammatory skin diseases (atopic dermatitis, lichen planus, contact eczema, and healthy controls). We identified a cluster of IL-17/TNFα-associated genes specifically expressed in psoriasis, among which IL-36γ was the most outstanding marker. In subsequent immunohistological analyses IL-36γ was confirmed to be expressed in psoriasis lesions only. IL-36γ peripheral blood serum levels were found to be closely associated with disease activity, and they decreased after anti-TNFα-treatment. Furthermore, IL-36γ immunohistochemistry was found to be a helpful marker in the histological differential diagnosis between psoriasis and eczema in diagnostically challenging cases. These features highlight IL-36γ as a valuable biomarker in psoriasis patients, both for diagnostic purposes and measurement of disease activity during the clinical course. Furthermore, IL-36γ might also provide a future drug target, due to its potential amplifier role in TNFα- and IL-17 pathways in psoriatic skin inflammation. In recent years, different genes and proteins have been highlighted as potential biomarkers for psoriasis, one of the most common inflammatory skin diseases worldwide. However, most of these markers are not psoriasis-specific but also found in other inflammatory disorders. We performed an unsupervised cluster analysis of gene expression profiles in 150 psoriasis patients and other inflammatory skin diseases (atopic dermatitis, lichen planus, contact eczema, and healthy controls). We identified a cluster of IL-17/TNFα-associated genes specifically expressed in psoriasis, among which IL-36γ was the most outstanding marker. In subsequent immunohistological analyses IL-36γ was confirmed to be expressed in psoriasis lesions only. IL-36γ peripheral blood serum levels were found to be closely associated with disease activity, and they decreased after anti-TNFα-treatment. Furthermore, IL-36γ immunohistochemistry was found to be a helpful marker in the histological differential diagnosis between psoriasis and eczema in diagnostically challenging cases. These features highlight IL-36γ as a valuable biomarker in psoriasis patients, both for diagnostic purposes and measurement of disease activity during the clinical course. Furthermore, IL-36γ might also provide a future drug target, due to its potential amplifier role in TNFα- and IL-17 pathways in psoriatic skin inflammation.
2014-12-02 | GSE63741 | GEO