Mutation p.N34S in SPINK1 may predispose patients to acute pancreatitis, especially in those abusing alcohol, and may promote a more severe course of the disease.
The p.N34S mutation in SPINK1 gene was found more frequently in patients with AP in the Indian population, irrespective of disease etiology and whether the disease was recurrent or not, and was associated with disease onset at an earlier age.
The SPINK1 variant p.N34S is overrepresented in patients with acute pancreatitis, but more studies distinguishing between first-time and recurrent acute pancreatitis have to be done to determine whether this is only true for patients with recurrent acute pancreatitis.
Patients bearing the N34S G allele exhibited a 10-fold increased risk of developing AP compared with controls, suggesting that the SPINK1N34S mutation represents an etiologic risk factor for AP in our Mexican pediatric patients.
The aim of this study was to investigate the association of cystic fibrosis transmembrane conductance regulator (CFTR) and serine protease inhibitor Kazal type 1 (SPINK-1) gene mutations and monocyte chemoattractant protein 1 (MCP-1) -2518A/G polymorphism with acute pancreatitis (AP), acute recurrent pancreatitis (ARP), and chronic pancreatitis (CP), and to associate genetic backgrounds with clinical phenotype in these three conditions.
This supports the importance of premature protease activation in the pathogenesis of AP and suggests that mutated SPINK1 may predispose certain individuals to develop this disease.
Attacks of acute pancreatitis in HP subjects appear to be independent of the relative expression of the mutant PRSS1 H122 allele or SPINK1 gene expression.
However, based on recent reports regarding various pathophysiological mechanisms for both acute pancreatitis and the Netherton syndrome (eg, shearing the 5q locus for the respective gene-associated defects in SPINK1 and SPINK5), we speculate if a possible association may exist.