Evidence map›Paper›PMID 21637341›Full record

ArticlePloS one2011

Allele-specific, age-dependent and BMI-associated DNA methylation of human MCHR1.

Stefanie Stepanow, Kathrin Reichwald, Klaus Huse, Ulrike Gausmann, Almut Nebel, Philip Rosenstiel, Martin Wabitsch, Pamela Fischer-Posovszky, Matthias Platzer

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 1 pooled it
3.2field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.

  1. Epigenetics and human obesity.International journal of obesity (2005) · 2015
    Pooled it
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  12. Epigenomics, gestational programming and risk of metabolic syndrome.International journal of obesity (2005) · 2015
    Review
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  15. Epigenomics of Alzheimer's disease.Translational research : the journal of laboratory and clinical medicine · 2015
    Review
  16. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 1 country.

Stefanie StepanowGenome Analysis, Leibniz Institute for Age Research, Jena, Germany. stepanow@fli-leibniz.de
Kathrin Reichwald
Klaus Huse
Ulrike Gausmann
Almut Nebel
Philip Rosenstiel
Martin Wabitsch
Pamela Fischer-Posovszky
Matthias Platzer
Leibniz Institute on Aging - Fritz Lipmann Institute (FLI) · DEKiel University · DEUniversität Ulm · DELeibniz Association · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMelanin-concentrating hormone receptor 1 (MCHR1) plays a significant role in regulation of energy balance, food intake, physical activity and body weight in humans and rodents. Several association studies for human obesity showed contrary results concerning the SNPs rs133072 (G/A) and rs133073 (T/C), which localize to the first exon of MCHR1. The variations constitute two main haplotypes (GT, AC). Both SNPs affect CpG dinucleotides, whereby each haplotype contains a potential methylation site at one of the two SNP positions. In addition, 15 CpGs in close vicinity of these SNPs constitute a weak CpG island. Here, we studied whether DNA methylation in this sequence context may contribute to population- and age-specific effects of MCHR1 alleles in obesity. PRINCIPAL

findingsWe analyzed DNA methylation of a 315 bp region of MCHR1 encompassing rs133072 and rs133073 and the CpG island in blood samples of 49 individuals by bisulfite sequencing. The AC haplotype shows a significantly higher methylation level than the GT haplotype. This allele-specific methylation is age-dependent. In young individuals (20-30 years) the difference in DNA methylation between haplotypes is significant; whereas in individuals older than 60 years it is not detectable. Interestingly, the GT allele shows a decrease in methylation status with increasing BMI, whereas the methylation of the AC allele is not associated with this phenotype. Heterozygous lymphoblastoid cell lines show the same pattern of allele-specific DNA methylation. The cell line, which exhibits the highest difference in methylation levels between both haplotypes, also shows allele-specific transcription of MCHR1, which can be abolished by treatment with the DNA methylase inhibitor 5-aza-2'-deoxycytidine.

conclusionsWe show that DNA methylation at MCHR1 is allele-specific, age-dependent, BMI-associated and affects transcription. Conceivably, this epigenetic regulation contributes to the age- and/or population specific effects reported for MCHR1 in several human obesity studies.

Indexed as

AllelesBody Mass IndexAdultAgedAgingAzacitidineCell LineCpG IslandsDNA MethylationGene Expression RegulationGenome, HumanHumansMaleMiddle AgedReceptors, SomatostatinRNA, MessengerAzacitidineMCHR1 protein, humanReceptors, SomatostatinRNA, Messenger

Identifiers

PMID21637341
PMCPMC3102661
OpenAlexW2046155613

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.