Evidence map›Paper›PMID 24451227›Full record

ArticleJournal of human genetics2014

p.Arg75Gln, a CFTR variant involved in the risk of CFTR-related disorders?

Brigitte Martinez, Marion Heller, Natacha Gaitch, Dominique Hubert, Pierre-Regis Burgel, Philippe Levy, Emmanuelle Girodon, Thierry Bienvenu

Open access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in Journal of human genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
1.0field-weighted citation impact, top 23% 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

3 citing papers in PubMed, 1 synthesis or guideline pooled it, 10 citations in OpenAlex.

  1. Pooled it
  2. Observational
  3. 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

8 authors at 3 institutions in 1 country.

Brigitte MartinezLaboratoire de Biochimie et Génétique Moléculaire, GH Cochin-Broca-Hôtel Dieu, AP-HP, Paris, France.
Marion HellerLaboratoire de Biochimie et Génétique Moléculaire, GH Cochin-Broca-Hôtel Dieu, AP-HP, Paris, France.
Natacha GaitchLaboratoire de Biochimie et Génétique Moléculaire, GH Cochin-Broca-Hôtel Dieu, AP-HP, Paris, France.
Dominique HubertService de Pneumologie, GH Cochin-Broca-Hôtel Dieu and Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
Pierre-Regis BurgelService de Pneumologie, GH Cochin-Broca-Hôtel Dieu and Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
Philippe LevyPôle des Maladies de l'Appareil Digestif, Service de Gastroentérologie-Pancréatologie, Hôpital Beaujon, AP-HP, Université Paris VII-Denis Diderot, Clichy, France.
Emmanuelle GirodonLaboratoire de Biochimie et Génétique Moléculaire, GH Cochin-Broca-Hôtel Dieu, AP-HP, Paris, France.
Thierry Bienvenu1] Laboratoire de Biochimie et Génétique Moléculaire, GH Cochin-Broca-Hôtel Dieu, AP-HP, Paris, France [2] Institut Cochin, INSERM U1016, Université Paris Descartes Paris, Paris, France.
Assistance Publique – Hôpitaux de Paris · FRUniversité Paris Cité · FRDélégation Paris 5 · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

c.224G>A, p.Arg75Gln (R75Q) presumably leads to an amino-acid change from arginine to glutamine in the membrane-spanning domain of the CFTR protein. Initially reported as a benign sequence variation, p.Arg75Gln was shown to be associated with a high risk of pancreatitis, a risk that was strikingly higher when p.Arg75Gln was combined with a SPINK1 variant. In addition, it was shown that p.Arg75Gln alters bicarbonate but not chloride conductance and that the mutation also induces exon 3 skipping. To investigate the role of p.Arg75Gln in idiopathic chronic pancreatitis (ICP), we performed genotyping of the CFTR gene in 880 patients with ICP, 198 patients with idiopathic bronchiectasis (IB), 74 patients with classical cystic fibrosis (CF), 48 patients with congenital bilateral absence of the vas deferens (CBAVD) and 148 healthy controls. p.Arg75Gln variant was identified in 3.3% (29/880) of patients with ICP, 3.3% (9/272) patients with a pulmonary disease, 2.1% (1/48) of patients with CBAVD and 4.7% (7/148) of healthy controls. It was frequently associated with the c.[1210-12T[7];1408A>G] (T7-p.Val470) allele and this CFTR genetic background could not explain the putative pathogenicity of this variant. To assess whether CFTR and SPINK1 mutations are co-inherited in pancreatitis, we sequenced SPINK1 gene exon 3 in the 46 patients who were previously identified to be heterozygous for p.Arg75Gln. Two SPINK1 pancreatitis-associated variants, p.Asn34Ser and p.Pro55Ser, were found in 6 patients: 4 of 29 (13.8%) patients with ICP (3 p.Asn34Ser and 1 p.Pro55Ser), 1 of 7 (14.3%) healthy controls (p.Asn34Ser) and 1 of 9 (11.1%) patients with IB (p.Pro55Ser). Our study does not confirm that the CFTR p.Arg75Gln mutation confers a significant risk of pancreatitis both when considered individually and with a concurrent SPINK1 mutation, suggesting the role of other genetic and environmental factors.

Indexed as

BronchiectasisCarrier ProteinsCase-Control StudiesCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorExonsGenetic Association StudiesHumansMale Urogenital DiseasesMutationPancreatitis, ChronicRiskRisk FactorsTrypsin Inhibitor, Kazal PancreaticVas DeferensCarrier ProteinsCFTR protein, humanCystic Fibrosis Transmembrane Conductance RegulatorSPINK1 protein, humanTrypsin Inhibitor, Kazal Pancreatic

Identifiers

PMID24451227
OpenAlexW1965267984

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.