Evidence map›Paper›PMID 28081267›Full record

Observational studyPloS one2017

Single Nucleotide Variants of Candidate Genes in Aggrecan Metabolic Pathway Are Associated with Lumbar Disc Degeneration and Modic Changes.

Romain Shanil Perera, Poruwalage Harsha Dissanayake, Upul Senarath, Lalith Sirimevan Wijayaratne, Aranjan Lional Karunanayake, Vajira Harshadeva Weerabaddana Dissanayake

Open access · goldAbstract readObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 2 pooled it
1.5field-weighted citation impact, top 19% 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

9 citing papers in PubMed, 2 syntheses or guidelines pooled it, 19 citations in OpenAlex.

  1. Pooled it
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  5. Review
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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

6 authors at 4 institutions in 1 country.

Romain Shanil PereraDepartment of Allied Health Sciences, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka.ORCID http://orcid.org/0000-0002-9682-5642
Poruwalage Harsha DissanayakeDepartment of Anatomy, Faculty of Medical Sciences, University of Sri Jayewardenepura, Gangodawila, Nugegoda, Sri Lanka.
Upul SenarathDepartment of Community Medicine, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka.
Lalith Sirimevan WijayaratneNational Hospital of Sri Lanka, Colombo, Sri Lanka.
Aranjan Lional KarunanayakeDepartment of Anatomy, Faculty of Medicine, University of Kelaniya, Ragama, Sri Lanka.
Vajira Harshadeva Weerabaddana DissanayakeHuman Genetics Unit, Department of Anatomy, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka.
University of Colombo · LKNational Hospital of Sri Lanka · LKUniversity of Kelaniya · LKUniversity of Sri Jayewardenepura · LK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionLumbar disc degeneration (LDD) is genetically determined and severity of LDD is associated with Modic changes. Aggrecan is a major proteoglycan in the intervertebral disc and end plate. Progressive reduction of aggrecan is a main feature of LDD and Modic changes.

objectivesThe study investigated the associations of single nucleotide variants (SNVs) of candidate genes in the aggrecan metabolic pathway with the severity of LDD and Modic changes. In-silico functional analysis of significant SNVs was also assessed.

methodsA descriptive cross sectional study was carried out on 106 patients with chronic mechanical low back pain. T1, T2 sagittal lumbar MRI scans were used to assess the severity of LDD and Modic changes. 62 SNVs in ten candidate genes (ACAN, IL1A, IL1B, IL6, MMP3, ADAMTS4, ADAMTS5, TIMP1, TIMP2 and TIMP3) were genotyped on Sequenom MassARRAY iPLEX platform. Multiple linear regression analysis was carried out using PLINK 1.9 in accordance with additive genetic model. In-silico functional analysis was carried out using Provean, SIFT, PolyPhen and Mutation Taster.

resultsMean age was 52.42±9.42 years. 74 (69.8%) were females. The rs2856836, rs1304037, rs17561 and rs1800587 variants of the IL1A gene were associated with the severity of LDD and Modic changes. The rs41270041 variant of the ADAMTS4 gene and the rs226794 variant of the ADAMTS5 gene were associated with severity of LDD while the rs34884997 variant of the ADAMTS4 gene, the rs55933916 variant of the ADAMTS5 gene and the rs9862 variant of the TIMP3 gene were associated with severity of Modic changes. The rs17561 variant of the IL1A gene was predicted as pathogenic by the PolyPhen prediction tool.

conclusionsSNVs of candidate genes in ACAN metabolic pathway are associated with severity of LDD and Modic changes in patients with chronic mechanical low back pain. Predictions of in-silico functional analysis of significant SNVs are inconsistent.

Indexed as

Polymorphism, Single NucleotideADAMTS4 ProteinADAMTS5 ProteinAdultAggrecansChronic PainFemaleHumansInterleukin-1alphaIntervertebral Disc DegenerationIntervertebral Disc DisplacementLow Back PainMaleMiddle AgedTissue Inhibitor of Metalloproteinase-3ACAN protein, humanADAMTS4 ProteinADAMTS4 protein, humanADAMTS5 ProteinADAMTS5 protein, humanAggrecansIL1A protein, humanInterleukin-1alphaTIMP3 protein, humanTissue Inhibitor of Metalloproteinase-3

Identifiers

PMID28081267
PMCPMC5231268
OpenAlexW2578442509

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.