RELATION BETWEEN MUTATIONS OF THE CYSTIC-FIBROSIS GENE AND IDIOPATHICPANCREATITIS

Background It is unknown whether genetic factors predispose patients t o idiopathic pancreatitis, In patients with cystic fibrosis, mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gen e typically cause pulmonary and pancreatic insufficiency while rarely causing pancreatitis. We examined whether idiopathic pancreatitis is a ssociated with CFTR mutations in persons who do not have lung disease of cystic fibrosis. Methods We studied 27 patients (mean age at diagno sis, 36 years), 22 of whom were female, who had been referred for an e valuation of idiopathic pancreatitis. DNA was tested for 17 CFTR mutat ions and for the 5T allele in intron 8 of the CFTR gene. The 5T allele reduces the level of functional CFTR and is associated with an inheri ted form of infertility in males. Patients with two abnormal CFTR alle les were further evaluated for unrecognized cystic fibrosis-related lu ng disease, and bath base-line and CFTR-mediated ion transport were me asured in the nasal mucosa. Results Ten patients with idiopathic chron ic pancreatitis (37 percent) had at least one abnormal CFTR allele. Ei ght CFTR mutations were detected (prevalence ratio, 11:1; 95 percent c onfidence interval, 5 to 23; P<0.001). In three patients both alleles were affected (prevalence ratio, 80:1; 95 percent confidence interval, 17 to 379; P<0.001). These three patients did not have lung disease t ypical of cystic fibrosis on the basis of sweat testing, spirometry, o r base-line nasal potential-difference measurements. Nonetheless, each had abnormal nasal cyclic AMP-mediated chloride transport. Conclusion s In a group of patients referred for evaluation of idiopathic pancrea titis, there was a strong association between mutations in the CFTR ge ne and pancreatitis. The abnormal CFTR genotypes in these patients wit h pancreatitis resemble those associated with male infertility. (N Eng l J Med 1998;339:653-8.) (C) 1998, Massachusetts Medical Society.