We analyzed CPA1, encoding carboxypeptidase A1, in subjects with nonalcoholic chronic pancreatitis (cases) and controls in a German discovery set and three replication sets.
The best characterized misfolding variants in the highly expressed digestive proteases cationic trypsinogen (PRSS1) and carboxypeptidase A1 (CPA1) are strong, causative risk factors for chronic pancreatitis and may be associated with autosomal dominant hereditary pancreatitis.
F508 deletion in CFTR was significantly positively associated with CP risk in the overall analysis (odds ratio [OR]=3.20, 95% CI: 2.30-4.44, I<sup>2</sup>=31.7%).
We here examined the prevalence of the serine protease inhibitor Kazal type 1 (SPINK1) gene mutations in Japanese patients with CP, and whether the disease course was different between mutation-positive and -negative patients.
PRSS1 mutations were identified mainly in CP patients (9.6% of CP vs 2.5% of ARP alleles, P = 0.094), whereas N34SSPINK1 mutation was present with comparable frequency in CP and ARP patients (7.7% vs 10.0%, P = 0.768).
While CFTR modulation has been shown to alkalinize the pH of the alimentary tract and potentially augment pancreatic enzyme activity, the effect of ivacaftor on recurrent pancreatitis is emerging.
Recent studies have shown an association between the N34S mutation in the serine protease inhibitor Kazal type 1 (SPINK1) gene and chronic pancreatitis (CP).
SPINK1 can inhibit up to 20% of trypsin activity, and may constitute one major mechanism to protect the pancreas from autodigestion.In 2000, Witt et al. first recognized the association between mutations in the SPINK1 gene and chronic pancreatitis (CP), but the significance of SPINK1 gene mutation in pancreatitis and its relation to alcohol consumption remains unclear in Japan.
We describe the case of a middle-aged male who presented with recurrent pancreatitis in the setting of the serine peptidase inhibitor, Kazal type 1 (SPINK-1) genetic polymorphism.
On multivariate analysis idiopathic etiology (p<0.03), presence of SPINK1 mutation (p=0.01), longer follow-up (p<0.001) were associated with progression to CP.
A genome-wide association study reported an association of chronic pancreatitis (CP) with variants in PRSS1-PRSS2 (rs10273639; near the gene encoding cationic trypsinogen) and CLDN2-MORC4 loci (rs7057398 in RIPPLY1 and rs12688220 in MORC4).
A cohort of 19 families (n=170) with a history of idiopathic CP (ICP) was screened for mutations within the CASR gene; 104 members of that cohort had a mutation (N34S) within the SPINK1 gene and 66 of those were suffering from CP.
Those preliminary data suggest low prevalence of SPINK1 and PRSS1 mutations in the Chinese population, generally, as well as in CP patients, indicating that these mutations do not contribute to the development of CP.
Despite these accomplishments, the understanding of the molecular mechanisms through which PRSS1 and SPINK1 mutations cause chronic pancreatitis has remained sketchy.
Those preliminary data suggest low prevalence of SPINK1 and PRSS1 mutations in the Chinese population, generally, as well as in CP patients, indicating that these mutations do not contribute to the development of CP.