Mannose-Binding Lectin (MBL) and Gap Junction Protein Alpha 4 (GJA4) Gene Heterogeneity in Relation to Severity of Clinical Disease in Cystic Fibrosis.
bronchial inflammation
cystic fibrosis
delta F 508 homozygous
gap junction protein alpha 4 (GJA4)
gene-gene interaction
mannose-binding lectin
Journal
Frontiers in bioscience (Landmark edition)
ISSN: 2768-6698
Titre abrégé: Front Biosci (Landmark Ed)
Pays: Singapore
ID NLM: 101612996
Informations de publication
Date de publication:
30 05 2022
30 05 2022
Historique:
received:
30
12
2021
revised:
15
02
2022
accepted:
17
02
2022
entrez:
24
6
2022
pubmed:
25
6
2022
medline:
28
6
2022
Statut:
ppublish
Résumé
Recently, we provided evidence that a single nucleotide polymorphism (SNP), rs41266431, on the gap junction protein alpha 4 (GJA4) gene, acts as a modifier for clinical disease severity in patients with cystic fibrosis (CF). These features are very similar to those of variants of the mannose-binding lectin (MBL). This study aimed to clarify whether the clinical disease phenotype associated with GJA4 variants is independent of MBL variants. One hundred and twelve patients with homozygous F508del (mean age, 27.6 years; m/f, 61/51) were recruited from the CF centers of Bonn, Frankfurt, and Amsterdam. A sequence analysis was performed for GJA4 and MBL. The clinical phenotype was assessed over three years using pulmonary function tests, body mass index, A clinically relevant SNP of GJA4 was identified by sequence analysis. Pulmonary function (FVC% pred, mean 78/85; The clinical disease phenotype associated with GJA4 variants is independent of MBL variants. MBL-sufficient variants were associated with superior BMI and a trend for better survival than MBL insufficient variants.
Sections du résumé
BACKGROUND
Recently, we provided evidence that a single nucleotide polymorphism (SNP), rs41266431, on the gap junction protein alpha 4 (GJA4) gene, acts as a modifier for clinical disease severity in patients with cystic fibrosis (CF). These features are very similar to those of variants of the mannose-binding lectin (MBL). This study aimed to clarify whether the clinical disease phenotype associated with GJA4 variants is independent of MBL variants.
METHODS
One hundred and twelve patients with homozygous F508del (mean age, 27.6 years; m/f, 61/51) were recruited from the CF centers of Bonn, Frankfurt, and Amsterdam. A sequence analysis was performed for GJA4 and MBL. The clinical phenotype was assessed over three years using pulmonary function tests, body mass index,
RESULTS
A clinically relevant SNP of GJA4 was identified by sequence analysis. Pulmonary function (FVC% pred, mean 78/85;
CONCLUSIONS
The clinical disease phenotype associated with GJA4 variants is independent of MBL variants. MBL-sufficient variants were associated with superior BMI and a trend for better survival than MBL insufficient variants.
Identifiants
pubmed: 35748244
pii: S2768-6701(22)00527-5
doi: 10.31083/j.fbl2706168
doi:
Substances chimiques
Connexins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
168Informations de copyright
© 2022 The Author(s). Published by IMR Press.
Déclaration de conflit d'intérêts
(1) Sabina Schmitt-Grohé is on the advisory committee of Vertex and has received a travel grant from Vertex (for ECFS 2019) and ERS (ERS Research Seminars). Moreover, she gave a talk to Vertex, participated in studies for the same, received a fee for a congress report (ECFS conference Liverpool 2019), and attended a vertex-sponsored conference (1.CF-Akademie, Schloss Hohenkammer). In addition, she got financial reimbursement for a talk for Deutsche CF Hilfe and received a personal fee for an expert opinion for the Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen.