Evidence map›Paper›PMID 34525218›Full record

ArticleAllergy2022

Single-base editing of rs12603332 on chromosome 17q21 with a cytosine base editor regulates ORMDL3 and ATF6α expression.

Ning Weng, Marina Miller, Alexa K Pham, Alexis C Komor, David H Broide

Open access · greenAbstract read
In one paragraph

Article in Allergy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.4field-weighted citation impact, top 40% 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

5 citing papers in PubMed, 9 citations in OpenAlex.

  1. Article
  2. Article
  3. Frontiers in genetics · 2026
    Review
  4. Update on the genetics of allergic diseases.The Journal of allergy and clinical immunology · 2025
    Review
  5. Review
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

5 authors at 1 institution in 1 country.

Ning WengDepartment of Medicine, University of California San Diego, La Jolla, California, USA.
Marina MillerDepartment of Medicine, University of California San Diego, La Jolla, California, USA.
Alexa K PhamDepartment of Medicine, University of California San Diego, La Jolla, California, USA.
Alexis C KomorDepartment of Chemistry and Biochemistry, University of California San Diego, La Jolla, California, USA.
David H BroideDepartment of Medicine, University of California San Diego, La Jolla, California, USA.ORCID 0000-0001-8405-9090
University of California San Diego · US

Funding

TRM and airway inflammation and remodelingU19AI070535 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BROIDE, DAVID H · 2006 to 2025
$34.2M
TRAINING IN MOLECULAR &CELL BIOLOGY OF ALLERGYT32AI007469 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BROIDE, DAVID H · 1994 to 2024
$6.9M
Chromosome 17q, allergic inflammation, and remodelingR01AI107779 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BROIDE, DAVID H · 2013 to 2024
$4.7M
GSDMB and mucosal allergic responseR01AI124236 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BROIDE, DAVID H · 2017 to 2020
$2.4M
NIAID NIH HHS R01 AI107779NIAID NIH HHS R01 AI124236NIAID NIH HHS T32 AI007469NIAID NIH HHS U19 AI070535
6 · The paper itself

Abstract

backgroundGenetic association studies have demonstrated that the SNP rs12603332 located on chromosome 17q21 is highly associated with the risk of the development of asthma.

methodsTo determine whether SNP rs1260332 is functional in regulating levels of ORMDL3 expression, we used a Cytosine Base Editor (CBE) plasmid DNA or a CBE mRNA to edit the rs12603332 C risk allele to the T non-risk allele in a human lymphocyte cell line (i.e., Jurkat cells) and in primary human CD4 T cells that carry the C risk alleles.

resultsJurkat cells with the rs12603332 C risk allele expressed significantly higher levels of ORMDL3 mRNA, as well as the ORMDL3 regulated gene ATF6α as assessed by qPCR compared to Jurkat clones with the T non-risk allele. In primary human CD4 T cells, we edited 90 ± 3% of the rs12603332-C risk allele to the T non-risk allele and observed a reduction in ORMDL3 and ATF6α expression. Bioinformatic analysis predicted that the non-risk allele rs12603332-T could be the central element of the E-box binding motif (CANNTG) recognized by the E47 transcription factor. An EMSA assay confirmed the bioinformatics prediction demonstrating that a rs12603332-T containing probe bound to the transcription factor E47 in vitro.

conclusionsSNP rs12603332 is functional in regulating the expression of ORMDL3 as well as ORMDL3 regulated gene ATF6α expression. In addition, we demonstrate the use of CBE technology in functionally interrogating asthma-associated SNPs using studies of primary human CD4 cells.

Indexed as

AsthmaChromosomes, Human, Pair 17CytosineCase-Control StudiesChromosomesGenetic Predisposition to DiseaseHumansMembrane ProteinsPolymorphism, Single NucleotideRNA, MessengerTranscription FactorsCytosineMembrane ProteinsORMDL3 protein, humanRNA, MessengerTranscription FactorsasthmaCRISPRCytosine Base EditorORMDL3SNP

Identifiers

PMID34525218
PMCPMC8920947
OpenAlexW3199558358

What OpenQuestion holds

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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.