Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in pancreatitis

被引:80
|
作者
Ooi, Chee Y. [1 ,2 ]
Durie, Peter R. [3 ,4 ,5 ]
机构
[1] Univ New S Wales, Fac Med, Sch Womens & Childrens Hlth, Sydney, NSW, Australia
[2] Sydney Childrens Hosp Randwick, Dept Gastroenterol, Sydney, NSW, Australia
[3] Hosp Sick Children, Res Inst, Toronto, ON M5G 1X8, Canada
[4] Hosp Sick Children, Dept Pediat, Div Gastroenterol Hepatol & Nutr, Toronto, ON M5G 1X8, Canada
[5] Univ Toronto, Dept Pediat, Toronto, ON M5S 1A1, Canada
关键词
Cystic fibrosis; Cystic fibrosis transmembrane conductance regulator; Pancreatitis; Pancreatic insufficiency; Pancreatic sufficiency; Cancer; EXOCRINE PANCREAS; IDIOPATHIC PANCREATITIS; RISK; SECRETION; DIAGNOSIS; GENOTYPE; CHANNELS;
D O I
10.1016/j.jcf.2012.05.001
中图分类号
R56 [呼吸系及胸部疾病];
学科分类号
摘要
Background: The pancreas is one of the primary organs affected by dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) protein. While exocrine pancreatic insufficiency is a well-recognized complication of cystic fibrosis (CF), symptomatic pancreatitis is often under-recognized. Results: The aim of this review is to provide a general overview of CFTR mutation-associated pancreatitis, which affects patients with pancreatic sufficient CF, CFTR-related pancreatitis, and idiopathic pancreatitis. The current hypothesis regarding the role of CFTR dysfunction in the pathogenesis of pancreatitis, and concepts on genotype phenotype correlations between CFTR and symptomatic pancreatitis will be reviewed. Symptomatic pancreatitis occurs in 20% of pancreatic sufficient CF patients. In order to evaluate genotype phenotype correlations, the Pancreatic Insufficiency Prevalence (PIP) score was developed and validated to determine severity in a large number of CFTR mutations. Specific CFTR genotypes are significantly associated with pancreatitis. Patients who carry genotypes with mild phenotypic effects have a greater risk of developing pancreatitis than patients carrying genotypes with moderate severe phenotypic consequences at any given time. Conclusions: The genotype phenotype correlation in pancreatitis is unique compared to other organ manifestations but still consistent with the complex monogenic nature of CF. Paradoxically, genotypes associated with otherwise mild phenotypic effects have a greater risk for causing pancreatitis; compared with genotypes associated with moderate to severe disease phenotypes. Greater understanding into the underlying mechanisms of disease is much needed. The emergence of CFTR-assist therapies may potentially play a future role in the treatment of CFTR-mutation associated pancreatitis. (C) 2012 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:355 / 362
页数:8
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