Evidence map›Paper›PMID 27253448›Full record

ArticleNeuron2016

Nuclear Receptor NR1H3 in Familial Multiple Sclerosis.

Zhe Wang, A Dessa Sadovnick, Anthony L Traboulsee, Jay P Ross, Cecily Q Bernales, Mary Encarnacion, Irene M Yee, Madonna de Lemos, Talitha Greenwood, Joshua D Lee and 5 more

Erratum issuedOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuron, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 48 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed, 1 pooled it
15.4field-weighted citation impact, top 1% 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

48 citing papers in PubMed, 1 synthesis or guideline pooled it, 98 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 1 institution in 1 country.

Zhe WangTownsend Family Laboratories, Department of Psychiatry, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
A Dessa SadovnickDepartment of Medical Genetics, University of British Columbia, Vancouver, BC V6T 1Z3, Canada; Division of Neurology, Faculty of Medicine, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
Anthony L TraboulseeDivision of Neurology, Faculty of Medicine, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
Jay P RossDepartment of Medical Genetics, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
Cecily Q BernalesDepartment of Medical Genetics, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
Mary EncarnacionDepartment of Medical Genetics, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
Irene M YeeDepartment of Medical Genetics, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
Madonna de LemosDepartment of Medical Genetics, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
Talitha GreenwoodDepartment of Medical Genetics, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
Joshua D LeeDepartment of Medical Genetics, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
Galen WrightDepartment of Medical Genetics, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
Colin J RossFaculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
Si ZhangTownsend Family Laboratories, Department of Psychiatry, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
Weihong SongTownsend Family Laboratories, Department of Psychiatry, University of British Columbia, Vancouver, BC V6T 1Z3, Canada. Electronic address: weihong@mail.ubc.ca.
Carles Vilariño-GüellDepartment of Medical Genetics, University of British Columbia, Vancouver, BC V6T 1Z3, Canada. Electronic address: carles@can.ubc.ca.
University of British Columbia · CA

Funding

CIHR 126949-1CIHR 137051-1
6 · The paper itself

Abstract

Multiple sclerosis (MS) is an inflammatory disease characterized by myelin loss and neuronal dysfunction. Despite the aggregation observed in some families, pathogenic mutations have remained elusive. In this study, we describe the identification of NR1H3 p.Arg415Gln in seven MS patients from two multi-incident families presenting severe and progressive disease, with an average age at onset of 34 years. Additionally, association analysis of common variants in NR1H3 identified rs2279238 conferring a 1.35-fold increased risk of developing progressive MS. The p.Arg415Gln position is highly conserved in orthologs and paralogs, and disrupts NR1H3 heterodimerization and transcriptional activation of target genes. Protein expression analysis revealed that mutant NR1H3 (LXRA) alters gene expression profiles, suggesting a disruption in transcriptional regulation as one of the mechanisms underlying MS pathogenesis. Our study indicates that pharmacological activation of LXRA or its targets may lead to effective treatments for the highly debilitating and currently untreatable progressive phase of MS.

Indexed as

AdultCase-Control StudiesFemaleGene ExpressionGenetic Predisposition to DiseaseHumansLiver X ReceptorsMaleMiddle AgedMultiple Sclerosis, Chronic ProgressiveMutationPedigreePhenotypeProtein IsoformsLiver X ReceptorsNR1H3 protein, humanProtein Isoforms

Identifiers

PMID27253448
PMCPMC5092154
OpenAlexW2415607391

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.