Abstract
BackgroundMutations in genes encoding cationic trypsinogen (PRSS1), pancreatic secretory trypsin inhibitor (SPINK1) and chymotrypsinogen C (CTRC) are associated with chronic pancreatitis. However, in many patients with a familial chronic pancreatitis pattern suggesting a genetic cause, no mutations in either of these genes can be found, indicating that other, still unknown, associated genes exist. In this respect ATP8B1 is an interesting candidate due to its strong expression in the pancreas, its supposed general function in membrane organization and the higher incidence of pancreatitis in patients with ATP8B1 deficiency.MethodsWe analyzed all 27 ATP8B1 coding exons and adjacent non-coding sequences of 507 chronic pancreatitis patients by direct sequencing. Exons that harbored possible relevant variations were subsequently sequenced in 1,027 healthy controls.ResultsIn the exonic regions, 5 novel non-synonymous alterations were detected as well as 14 previously described alterations of which some were associated with ATP8B1 deficiency. However, allele frequencies for any of these variations did not significantly differ between patients and controls. Furthermore, several non-synonymous variants were exclusively detected in control subjects and multiple variants in the non-coding sequence were identified with similar frequencies in both groups.ConclusionsWe did not find an association between heterozygous ATP8B1 variants and chronic pancreatitis in our cohort of patients with hereditary and idiopathic chronic pancreatitis.
Highlights
Chronic pancreatitis (CP) is an inflammatory disease characterized by destruction of pancreatic parenchyma that can result in permanent impairment of both exocrine and endocrine pancreatic function [1]
CP might cluster in families, and in many of these affected subjects as well as young patients without a family history of pancreatitis, mutations in the genes coding for cationic trypsinogen (PRSS1), pancreatic secretory trypsin inhibitor (SPINK1) and chymotrypsinogen C (CTRC) can be identified [2,3,4,5]
ATP8B1 deficiency can present with persistent cholestasis, usually at young age or with episodic cholestasis at any age
Summary
Chronic pancreatitis (CP) is an inflammatory disease characterized by destruction of pancreatic parenchyma that can result in permanent impairment of both exocrine and endocrine pancreatic function [1]. The benign variant will progress to the more severe and permanent form of intrahepatic cholestasis, indicative of a clinical continuum [8] Extrahepatic manifestations such as diarrhoea, pancreatitis and hearing loss can be observed in patients with ATP8B1 deficiency [9]. In many patients with a familial chronic pancreatitis pattern suggesting a genetic cause, no mutations in either of these genes can be found, indicating that other, still unknown, associated genes exist. In this respect ATP8B1 is an interesting candidate due to its strong expression in the pancreas, its supposed general function in membrane organization and the higher incidence of pancreatitis in patients with ATP8B1 deficiency
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