MUTATIONS OF THE CYSTIC-FIBROSIS GENE IN PATIENTS WITH CHRONIC-PANCREATITIS

Background The pancreatic lesions of cystic fibrosis develop in utero and closely resemble those of chronic pancreatitis. Therefore, we hypo thesized that mutations of the cystic fibrosis transmembrane conductan ce regulator (CFTR) gene may be more common than expected among patien ts with chronic pancreatitis. Methods We studied 134 consecutive patie nts with chronic pancreatitis (alcohol-related disease in 71, hyperpar athyroidism in 2, hypertriglyceridemia in 1, and idiopathic disease in 60). We examined DNA for 22 mutations of the CFTR gene that together account for 95 percent of all mutations in patients with cystic fibros is in the northwest of England. We also determined the length of the n oncoding sequence of thymidines in intron 8, since the shorter the seq uence, the lower the proportion of normal CFTR messenger RNA. Results The 94 male and 40 female patients ranged in age from 16 to 86 years. None had a mutation on both copies of the CFTR gene. Eighteen patients (13.4 percent), including 12 without alcoholism, had a CFTR mutation on one chromosome, as compared with a frequency of 5.3 percent among 6 00 local unrelated partners of persons with a family history of cystic fibrosis (P<0.001). A total of 10.4 percent of the patients had the 5 T allele in intron 8 (14 of 134), which is twice the expected frequenc y (P=0.008). Four patients were heterozygous for both a CFTR mutation and the 5T allele. Patients with a CFTR mutation were younger than tho se with no mutations (P=0.03). None had the combination of sinopulmona ry disease, high sweat electrolyte concentrations, and low nasal poten tial-difference values that are diagnostic of cystic fibrosis. Conclus ions Mutations of the CFTR gene and the 5T genotype are associated wit h chronic pancreatitis. (N Engl J Med 1998;339:645-52.) (C) 1998, Mass achusetts Medical Society.