Dataset Information

Bicarbonate defective CFTR variants increase risk for chronic pancreatitis: A meta-analysis.

ABSTRACT:

Introduction

Cystic fibrosis transmembrane conductance regulator (CFTR) plays a central role in pancreatic ductal fluid secretion by mediating Cl- and HCO3- ion transport across the apical membrane. Severe CFTR mutations that diminish chloride conductance cause cystic fibrosis (CF) if both alleles are affected, whereas heterozygous carrier status increases risk for chronic pancreatitis (CP). It has been proposed that a subset of CFTR variants characterized by a selective bicarbonate conductance defect (CFTRBD) may be associated with CP but not CF. However, a rigorous genetic analysis of the presumed association has been lacking.

Aims

To investigate the role of heterozygous CFTRBD variants in CP by meta-analysis of published case-control studies.

Materials and methods

A systematic search was conducted in the MEDLINE, Embase, Scopus, and CENTRAL databases for published studies that reported the CFTRBD variants p.R74Q, p.R75Q, p.R117H, p.R170H, p.L967S, p.L997F, p.D1152H, p.S1235R, and p.D1270N in CP patients and controls.

Results

Twenty-two studies were eligible for quantitative synthesis. Combined analysis of the 9 CFTRBD variants indicated enrichment in CP patients versus controls (OR = 2.31, 95% CI = 1.17-4.56). Individual analysis of CFTRBD variants revealed no association of p.R75Q with CP (OR = 1.12, 95% CI = 0.89-1.40), whereas variants p.R117H and p.L967S were significantly overrepresented in cases relative to controls (OR = 3.16, 95% CI = 1.94-5.14, and OR = 3.88, 95% CI = 1.32-11.47, respectively). The remaining 6 low-frequency variants gave inconclusive results when analyzed individually, however, their pooled analysis indicated association with CP (OR = 2.08, 95% CI = 1.38-3.13).

Conclusion

Heterozygous CFTRBD variants, with the exception of p.R75Q, increase CP risk about 2-4-fold.

SUBMITTER: Berke G

PROVIDER: S-EPMC9584382 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Bicarbonate defective CFTR variants increase risk for chronic pancreatitis: A meta-analysis.

Berke Gergő G Gede Noémi N Szadai Letícia L Ocskay Klementina K Hegyi Péter P Sahin-Tóth Miklós M Hegyi Eszter E

PloS one 20221020 10

<h4>Introduction</h4>Cystic fibrosis transmembrane conductance regulator (CFTR) plays a central role in pancreatic ductal fluid secretion by mediating Cl- and HCO3- ion transport across the apical membrane. Severe CFTR mutations that diminish chloride conductance cause cystic fibrosis (CF) if both alleles are affected, whereas heterozygous carrier status increases risk for chronic pancreatitis (CP). It has been proposed that a subset of CFTR variants characterized by a selective bicarbonate cond ...[more]

PMID: 36264955

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Dataset Information

Bicarbonate defective CFTR variants increase risk for chronic pancreatitis: A meta-analysis.

Introduction

Aims

Materials and methods

Results

Conclusion

Publications

Bicarbonate defective CFTR variants increase risk for chronic pancreatitis: A meta-analysis.

Similar Datasets

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