Evidence map›Paper›PMID 9769329›Full record

ArticleThe Journal of clinical investigation1998

The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis.

D Fishman, G Faulds, R Jeffery, V Mohamed-Ali, J S Yudkin, S Humphries, P Woo

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In one paragraph

Article in The Journal of clinical investigation, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 653 papers, 19 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
653citing papers in PubMed, 19 pooled it
19.8field-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

653 citing papers in PubMed, 19 syntheses or guidelines pooled it, 2,239 citations in OpenAlex.

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  5. Effects ofFrontiers in genetics · 2022
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  6. Uncovering Outcome Disparities of βJournal of the National Medical Association · 2021
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  18. Association ofBioscience reports · 2018
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  20. Trial

593 more citing papers are in PubMed but not listed here.

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

7 authors at 3 institutions in 3 countries.

D FishmanPaediatric Rheumatology Unit, Windeyer Institute of Medical Sciences, University College London Medical School, London W1P 6DB.
G Faulds
R Jeffery
V Mohamed-Ali
J S Yudkin
S Humphries
P Woo
University College London · GBInstitute of Medical Sciences · INWhittington Hospital · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

During active disease, patients with systemic-onset juvenile chronic arthritis (S-JCA) demonstrate a rise and fall in serum interleukin-6 (IL-6) that parallels the classic quotidian fever. To investigate the possibility that this cytokine profile results from a difference in the control of IL-6 expression, we examined the 5' flanking region of the IL-6 gene for polymorphisms. A G/C polymorphism was detected at position -174. In a group of 383 healthy men and women from a general practice in North London, the frequency of the C allele was 0.403 (95% confidence interval 0.37-0.44). In comparison, 92 patients with S-JCA had a different overall genotype frequency, especially those with onset of disease at < 5 yr of age. This was mainly due to the statistically significant lower frequency of the CC genotype in this subgroup. When comparing constructs of the 5' flanking region (-550-+61 bp) in a luciferase reporter vector transiently transfected into HeLa cells, the -174C construct showed 0.624+/-0.15-fold lower expression than the -174G construct. After stimulation with LPS or IL-1, expression from the -174C construct did not significantly change after 24 h, whereas expression from the -174G construct increased by 2.35+/-0.10- and 3.60+/-0.26-fold, respectively, compared with the unstimulated level. Plasma levels of IL-6 were also measured in 102 of the healthy subjects, and the C allele was found to be associated with significantly lower levels of plasma IL-6. These results suggest that there is a genetically determined difference in the degree of the IL-6 response to stressful stimuli between individuals. The reduced frequency of the potentially protective CC genotype in young S-JCA patients may contribute to its pathogenesis. Similarly the individual's IL-6 genotype may be highly relevant in other conditions where IL-6 has been implicated, such as atherosclerosis.

Indexed as

Polymorphism, GeneticTranscription, GeneticAdolescentAdultAgedAge of OnsetArthritis, JuvenileBase SequenceChildDNA PrimersFemaleGene Expression RegulationGene FrequencyGenotypeHeLa CellsHumansDNA PrimersInterleukin-6

Identifiers

PMID9769329
PMCPMC508984
OpenAlexW2089022749

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.