Epigenetic differences at the HTR2A locus in progressive multiple sclerosis patients
| Autor: | Rodney A. Lea, Nicole White, Kira Groen, Samara Bray, Jeannette Lechner-Scott, Thao Van Cao, Rodney J. Scott, Melissa Gresle, Vicki E. Maltby, Helmut Butzkueven, Louise Laverick, Daniel W. Kennedy, Sean Burnard, Rebecca G.Y. Seeto, Alexandre Xavier, Katherine A. Sanders |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Multiple Sclerosis Genotype Science Single-nucleotide polymorphism Biology Polymorphism Single Nucleotide Linkage Disequilibrium Article Epigenesis Genetic Medical research Humans Receptor Serotonin 5-HT2A Epigenetics Allele Alleles Aged Genetics Multidisciplinary Gene Expression Profiling Computational Biology High-Throughput Nucleotide Sequencing Methylation DNA Methylation Middle Aged Differentially methylated regions Gene Expression Regulation Genetic Loci DNA methylation Disease Progression Medicine Female Human genome Disease Susceptibility Transcriptome |
| Zdroj: | Scientific Reports, Vol 10, Iss 1, Pp 1-10 (2020) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | The pathology of progressive multiple sclerosis (MS) is poorly understood. We have previously assessed DNA methylation in the CD4+ T cells of relapsing–remitting (RR) MS patients compared to healthy controls and identified differentially methylated regions (DMRs) in HLA-DRB1 and RNF39. This study aimed to investigate the DNA methylation profiles of the CD4+ T cells of progressive MS patients. DNA methylation was measured in two separate case/control cohorts using the Illumina 450K/EPIC arrays and data was analysed with the Chip Analysis Methylation Pipeline (ChAMP). Single nucleotide polymorphisms (SNPs) were assessed using the Illumina Human OmniExpress24 arrays and analysed using PLINK. Expression was assessed using the Illumina HT12 array and analysed in R using a combination of Limma and Illuminaio. We identified three DMRs at HTR2A, SLC17A9 and HDAC4 that were consistent across both cohorts. The DMR at HTR2A is located within the bounds of a haplotype block; however, the DMR remained significant after accounting for SNPs in the region. No expression changes were detected in any DMRs. HTR2A is differentially methylated in progressive MS independent of genotype. This differential methylation is not evident in RRMS, making it a potential biomarker of progressive disease. |
| Databáze: | OpenAIRE |
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