Evidence map›Paper›PMID 33674211›Full record

Observational studyJournal of cystic fibrosis : official journal of the European Cystic Fibrosis Society2021

SLC26A9 SNP rs7512462 is not associated with lung disease severity or lung function response to ivacaftor in cystic fibrosis patients with G551D-CFTR.

Alice C Eastman, Rhonda G Pace, Hong Dang, Melis Atalar Aksit, Briana Vecchio-Pagán, Anh-Thu N Lam, Wanda K O'Neal, Scott M Blackman, Michael R Knowles, Garry R Cutting

Registry-linked trialOpen access · greenAbstract readObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00037765 (Gene Modifiers of Cystic Fibrosis Lung Disease), which is not on this map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.8field-weighted citation impact, top 15% 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.

NCT00037765 active not recruitingnot on this map

Gene Modifiers of Cystic Fibrosis Lung Disease

TypeobservationalSponsorUniversity of North Carolina, Chapel HillRan2001 to 2027Enrolled600ConditionsCystic Fibrosis, Lung Diseases
3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 14 citations in OpenAlex.

  1. Nucleotide Variant in theJournal of clinical medicine · 2026
    Article
  2. Review
  3. Review
  4. Modifier Factors of Cystic Fibrosis Phenotypes: A Focus on Modifier Genes.International journal of molecular sciences · 2022
    Review
  5. Article
  6. Article
  7. Review
  8. Article
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

10 authors at 2 institutions in 1 country.

Alice C EastmanDepartment of Genetic Medicine, Johns Hopkins University (JHU), Baltimore, MD, 21205, USA.
Rhonda G PaceUniversity of North Carolina at Chapel Hill (UNC), Chapel Hill, NC, 27599, USA.
Hong DangUniversity of North Carolina at Chapel Hill (UNC), Chapel Hill, NC, 27599, USA.
Melis Atalar AksitDepartment of Genetic Medicine, Johns Hopkins University (JHU), Baltimore, MD, 21205, USA.
Briana Vecchio-PagánDepartment of Genetic Medicine, Johns Hopkins University (JHU), Baltimore, MD, 21205, USA.
Anh-Thu N LamDepartment of Genetic Medicine, Johns Hopkins University (JHU), Baltimore, MD, 21205, USA.
Wanda K O'NealUniversity of North Carolina at Chapel Hill (UNC), Chapel Hill, NC, 27599, USA.
Scott M BlackmanDepartment of Genetic Medicine, Johns Hopkins University (JHU), Baltimore, MD, 21205, USA.
Michael R KnowlesUniversity of North Carolina at Chapel Hill (UNC), Chapel Hill, NC, 27599, USA. Electronic address: michael_knowles@med.unc.edu.
Garry R CuttingDepartment of Genetic Medicine, Johns Hopkins University (JHU), Baltimore, MD, 21205, USA. Electronic address: gcutting@jhmi.edu.
Johns Hopkins University · USUniversity of North Carolina at Chapel Hill · US

Funding

MOLECULAR GENETICS OF CYSTIC FIBROSISR01DK044003 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI Garry R Cutting · 1991 to 2026
$6.7M
NIDDK NIH HHS R01 DK044003
6 · The paper itself

Abstract

backgroundThe CFTR modulator ivacaftor has been variably effective in treating individuals with cystic fibrosis (CF) who harbor CFTR gating variants such as G551D, as well as other classes of CFTR variants when used with other modulators. Because CFTR genotype does not fully explain this variability, defining genetic modifiers of response to modulator therapy is of particular interest to the field of individualized CF drug therapy. Previous studies have proposed that a variant in SLC26A9 (rs7512462) is associated with lung disease severity and with response to treatment with ivacaftor in individuals with CF who carry G551D or gating variants.

methodsGiven the implications for CF treatment, we re-examined the reported associations in three cohorts; patients enrolled in the Twin and Siblings study at Johns Hopkins University, the CF modifier study at the University of North Carolina at Chapel Hill, and the prospective G551D Observational (GOAL) study. The GOAL study was specifically designed to measure lung function response to ivacaftor.

resultsWe find no association between SLC26A9 (rs7512462) genotype and lung disease severity (n = 272) or change in lung function at one-, three-, and six-month intervals following ivacaftor treatment(n = 141) in individuals with CF who carry at least one G551D variant.

conclusionsOur inability to replicate this association indicates that rs7512462 genotype should not be used in treatment decisions.

Indexed as

AminophenolsAntiportersCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorFemaleGenotypeHumansMalePolymorphism, Single NucleotideProspective StudiesQuinolonesRespiratory Function TestsSeverity of Illness IndexSulfate TransportersYoung AdultAminophenolsAntiportersCystic Fibrosis Transmembrane Conductance RegulatorivacaftorQuinolonesSLC26A9 protein, humanSulfate TransportersG551DIvacaftor efficacyModifier genesSLC26A9 rs7512462

Identifiers

PMID33674211
PMCPMC8410892
OpenAlexW3134023024

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

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.