Genetic, epidemiological, and clinical aspects of hereditary pancreatitis: a population-based cohort study in Denmark.
OBJECTIVE
In a population-based, well-defined group of patients first regarded as having pancreatitis of unknown origin (PUO), we identified, described, and compared the clinical and genetic aspects of patients with hereditary pancreatitis (HP) and with cystic fibrosis transmembrane conductance regulator gene (CFTR) and serine protease inhibitor Kazal type 1 gene (SPINK1) mutations with patients who retained the diagnosis of true idiopathic pancreatitis (tIP) after genetic testing for HP, SPINK1, and CFTR mutations.


METHODS
Patients with PUO were identified in the Danish National Registry of Patients or were referred by clinicians. DNA from blood was analyzed for cationic trypsinogen (PRSS1), SPINK1, and CFTR mutations. Considering the diagnosis of HP, a pedigree was drawn for each patient.


RESULTS
A genetic mutation was found in 40% of 122 patients with PUO. After testing first-degree relatives of the 18 initially identified HP patients, 38 HP patients in total were identified, and 28 patients had SPINK1-CFTR mutations. Among HP patients, no p.N29I mutations were found and the p.A16V mutation was more frequent than previously reported, 45 and 32% had exocrine and endocrine insufficiency, respectively, and among tIP patients 9 and 12%, respectively. Pancreatic cancer was diagnosed in 5% of the HP families.


CONCLUSIONS
The genotype of the Danish population with HP differs from that of previously described cohorts. The occurrence of exocrine and endocrine insufficiency is higher among patients with HP than in patients with SPINK1-CFTR mutations and tIP, and more HP families develop pancreatic cancer. Genetic testing thus helps to predict the prognosis of the pancreatitis.
Joergensen
Maiken Thyregod
MT
Department of Medical Gastroenterology, Odense University Hospital, University of Southern Denmark, Odense C, Denmark. maiken.t.joergensen@ouh.regionsyddanmark.dk
Brusgaard
Klaus
K
Crüger
Dorthe Gylling
DG
Gerdes
Anne-Marie
AM
Schaffalitzky de Muckadell
Ove B
OB
D000328:Adult; D002352:Carrier Proteins / Q000235:genetics*; D016009:Chi-Square Distribution; D015331:Cohort Studies; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D003718:Denmark / Q000453:epidemiology; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000453:epidemiology / Q000235:genetics; D010195:Pancreatitis / Q000453:epidemiology* / Q000235:genetics*; D010375:Pedigree; D016012:Poisson Distribution; D011379:Prognosis; D012042:Registries; D012307:Risk Factors; D018709:Statistics, Nonparametric; D014357:Trypsin / Q000235:genetics; D014359:Trypsin Inhibitor, Kazal Pancreatic
D002352:Carrier Proteins; C486642:SPINK1 protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D014359:Trypsin Inhibitor, Kazal Pancreatic; C489303:PRSS1 protein, human; D014357:Trypsin