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Differential methylation at MHC in CD4+ T cells is associated with multiple sclerosis independently of HLA-DRB1

Overview of attention for article published in Clinical Epigenetics, July 2017
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Title
Differential methylation at MHC in CD4+ T cells is associated with multiple sclerosis independently of HLA-DRB1
Published in
Clinical Epigenetics, July 2017
DOI 10.1186/s13148-017-0371-1
Pubmed ID
Authors

Vicki E. Maltby, Rodney A. Lea, Katherine A. Sanders, Nicole White, Miles C. Benton, Rodney J. Scott, Jeannette Lechner-Scott

Abstract

Although many genetic variants have been associated with multiple sclerosis (MS) risk, they do not explain all the disease risk and there remains uncertainty as to how these variants contribute to disease. DNA methylation is an epigenetic mechanism that can influence gene expression and has the potential to mediate the effects of environmental factors on MS. In a previous study, we found a differentially methylation region (DMR) at MHC HLA-DRB1 that was associated within relapsing-remitting MS (RRMS) patients in CD4(+) T cells. This study aimed to confirm this earlier finding in an independent RRMS cohort of treatment-naïve female patients. Total genomic DNA was extracted from CD4(+) T cells of 28 female RRMS and 22 age-matched healthy controls subjects. DNA was bisulfite-converted and hybridised to Illumina 450K arrays. Beta values for all CpGs were analysed using the DMPFinder function in the MINFI program, and a follow-up prioritisation process was applied to identify the most robust MS-associated DMRs. This study confirmed our previous findings of a hypomethylated DMR at HLA-DRB1 and a hypermethylated DMR at HLA-DRB5 in this RRMS patient cohort. In addition, we identified a large independent DMR at MHC, whereby 11 CpGs in RNF39 were hypermethylated in MS cases compared to controls (max. ∆beta = 0.19, P = 2.1 × 10(-4)). We did not find evidence that SNP genotype was influencing the DMR in this cohort. A smaller MHC DMR was also identified at HCG4B, and two non-MHC DMRs at PM20D1 on chr1 and ERICH1 on chr8 were also identified. The findings from this study confirm our previous results of a DMR at HLA-DRB1 and also suggest hypermethylation in an independent MHC locus, RNF39, is associated with MS. Taken together, our results highlight the importance of epigenetic factors at the MHC locus in MS independent of treatment, age and sex. Prospective studies are now required to discern whether methylation at MHC is involved in influencing risk of disease onset or whether the disease itself has altered the methylation profile.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 42 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 42 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 10 24%
Researcher 7 17%
Student > Bachelor 3 7%
Other 3 7%
Student > Ph. D. Student 3 7%
Other 5 12%
Unknown 11 26%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 12 29%
Medicine and Dentistry 6 14%
Agricultural and Biological Sciences 5 12%
Pharmacology, Toxicology and Pharmaceutical Science 1 2%
Unspecified 1 2%
Other 4 10%
Unknown 13 31%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 23 July 2017.
All research outputs
#14,355,715
of 22,988,380 outputs
Outputs from Clinical Epigenetics
#747
of 1,262 outputs
Outputs of similar age
#175,491
of 314,952 outputs
Outputs of similar age from Clinical Epigenetics
#15
of 30 outputs
Altmetric has tracked 22,988,380 research outputs across all sources so far. This one is in the 35th percentile – i.e., 35% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,262 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.5. This one is in the 37th percentile – i.e., 37% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 314,952 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 41st percentile – i.e., 41% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 30 others from the same source and published within six weeks on either side of this one. This one is in the 43rd percentile – i.e., 43% of its contemporaries scored the same or lower than it.