In:
PLOS ONE, Public Library of Science (PLoS), Vol. 17, No. 10 ( 2022-10-20), p. e0276397-
Abstract:
Cystic fibrosis transmembrane conductance regulator (CFTR) plays a central role in pancreatic ductal fluid secretion by mediating Cl - and HCO 3 - 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 ( CFTR BD ) 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 CFTR BD 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 CFTR BD 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 CFTR BD variants indicated enrichment in CP patients versus controls (OR = 2.31, 95% CI = 1.17–4.56). Individual analysis of CFTR BD 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 CFTR BD variants, with the exception of p.R75Q, increase CP risk about 2-4-fold.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0276397
DOI:
10.1371/journal.pone.0276397.g001
DOI:
10.1371/journal.pone.0276397.g002
DOI:
10.1371/journal.pone.0276397.g003
DOI:
10.1371/journal.pone.0276397.g004
DOI:
10.1371/journal.pone.0276397.s001
DOI:
10.1371/journal.pone.0276397.s002
DOI:
10.1371/journal.pone.0276397.s003
DOI:
10.1371/journal.pone.0276397.s004
DOI:
10.1371/journal.pone.0276397.s005
DOI:
10.1371/journal.pone.0276397.s006
DOI:
10.1371/journal.pone.0276397.s007
DOI:
10.1371/journal.pone.0276397.s008
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2267670-3
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