CFTR p.F508del Mutation Carrier Status Is Not Associated With Biliary Acute Pancreatitis

To the Editor: The cystic fibrosis transmembrane conductance regulator (CFTR) channel is highly expressed in the biliary tree and the gall bladder, and maintains biliary health through a protective “bicarbonate umbrella.”1 Cystic fibrosis (CF) disease caused by homozygous loss-of-function mutations in CFTR is associated with biliary disorders in a subset of patients.1,2 Therefore, we hypothesized that carrier status for a severe CF-causing CFTR mutation might increase risk for biliary acute pancreatitis. A Polish study found no association between the p.F508del CFTR variant and biliary acute pancreatitis; however, the investigated cohort was small.3 Here, we genotyped Hungarian patients with biliary acute pancreatitis, nonbiliary acute pancreatitis, and healthy controls for the c.1521_1523delCTT (p.F508del) mutation by direct Sanger sequencing of exon 11 in CFTR. Patients with chronic pancreatitis, those with recurrent acute pancreatitis with more than 2 attacks, and subjects older than 60 were excluded. The biliary pancreatitis cohort included 190 subjects (117 women); the mean age at time of admission was 43.8 years (standard deviation, 11.5 years; range, 18–60 years), the disease severity was mild in 151 cases (98 women), moderate in 34 cases (17 women), and severe in 5 cases (2 women). The nonbiliary pancreatitis cohort consisted of 178 patients (51 women); the mean age at time of admission was 44.3 years (standard deviation, 9.9 years; range, 18–60 years); and disease severity was mild in 105 cases, moderate in 62 cases, and severe in 11 cases. The etiology in this cohort was alcoholic in 81 subjects (6 women), idiopathic in 60 subjects (38 women), hypertriglyceridemia associated in 26 subjects (6 women), and post-endoscopic retrograde cholangiopancreatography complication in 11 subjects (1 woman). The control group included 197 subjects (74 women), and the mean age at the time of blood collection was 37 years (standard deviation, 8.5 years; range, 24–59 years). We found the heterozygous p.F508del variant in 6 of 190 patients (3 women) with biliary acute pancreatitis (3.2%), in 4 of 178 patients (all men) with nonbiliary acute pancreatitis (2.2%), and in 5 of 197 controls (2.5%, 1 woman). As expected, no homozygous p.F508del carriers were detected. All patients with p.F508del in the biliary group had mild disease, whereas in the nonbiliary group, 3 had mild disease (2 alcoholic, 1 idiopathic) and 1 had severe disease of alcoholic etiology. Comparison of carrier frequencies revealed no significant association of the p.F508del variant with acute pancreatitis. The calculated odds ratios (OR) with 95% confidence intervals (CI), and P values were as follows—biliary acute pancreatitis versus controls: OR, 1.25; 95% CI, 0.38–4.17, P = 0.71; nonbiliary acute pancreatitis versus controls: OR, 0.88; 95% CI, 0.23–3.34, P = 0.85; combined acute pancreatitis cohort versus controls: OR, 1.07; 95% CI, 0.36–3.18, P = 0.9. We conclude that heterozygous CF-causing CFTR mutations do not modify susceptibility for biliary acute pancreatitis. Ágnes Rita Martonosi, MDHeim Pál National Pediatric InstituteBudapest, HungaryDoctoral School of Clinical MedicineUniversity of SzegedSzeged, HungaryInstitute for Translational MedicineUniversity of Pécs Medical SchoolPécs, HungaryBalázs Csaba Németh, MD, PhDHungarian Centre of Excellence for MolecularMedicine University of SzegedTranslational Pancreatology Research GroupSzeged, HungaryDepartment of MedicineAlbert Szent-Györgyi Medical SchoolUniversity of SzegedSzeged, HungaryAndrea Párniczky, MD, PhDHeim Pál National Pediatric InstituteBudapest, HungaryInstitute for Translational MedicineUniversity of Pécs Medical SchoolPécs, HungaryCentre for Translational MedicineSemmelweis UniversityBudapest, HungaryÁron Vincze, MD, PhDDivision of GastroenterologyFirst Department of MedicineUniversity of Pécs Medical SchoolPécs, HungaryAndrea Szentesi, PhDInstitute for Translational MedicineUniversity of Pécs Medical SchoolPécs, HungaryBálint Erőss, MD, PhDInstitute for Translational MedicineUniversity of Pécs Medical SchoolPécs, HungaryCentre for Translational MedicineSemmelweis UniversityBudapest, HungaryInstitute of Pancreatic DiseasesSemmelweis UniversityBudapest, HungaryMiklós Sahin-Tóth, MD, PhDDepartment of SurgeryUniversity of California, Los AngelesLos Angeles, CAPéter Hegyi, MD, PhD, DSc, MAEInstitute for Translational MedicineUniversity of Pécs Medical SchoolPécs, HungaryCentre for Translational MedicineSemmelweis UniversityBudapest, HungaryInstitute of Pancreatic DiseasesSemmelweis UniversityBudapest, HungaryTranslational Pancreatology Research GroupInterdisciplinary Centre of Excellence forResearch Development and InnovationUniversity of SzegedSzeged, HungaryEszter Hegyi, MD, PhDDoctoral School of Clinical MedicineUniversity of SzegedSzeged, HungaryInstitute for Translational MedicineUniversity of Pécs Medical SchoolPécs, Hungaryeszter.hegyi@aok