Frequency of SPINK1 N34S mutation in acute and recurrent acute pancreatitis

Several studies have reported association of c.101A>G (p.N34S) mutation in SPINK1 gene with chronic pancreatitis; however, the data on its relationship with acute pancreatitis (AP) and recurrent acute pancreatitis (RAP) are limited.

We studied 183 unrelated patients with AP and RAP and 168 healthy controls for p.N34S variant in SPINK1 gene using sequencing of genomic DNA.

SPINK1 p.N34S mutation was found in four of 168 (2.4%; all heterozygotes) controls and 22 of 183 (12.0%; including one homozygote) patients with AP (P = 0.006). On subgroup analysis, seven of 70 (10.0%) patients with gallstone-related AP, eight of 59 (13.6%; including one homozygote) patients with idiopathic AP, and six of 44 (14.6%) patients with alcohol-related AP had the p.N34S mutation (P = 0.027, 0.002 and 0.006, respectively, compared to controls). Frequency of this mutation was similar in patients with one episode of AP and those with recurrent AP (12% each). The first attack of AP occurred earlier in patients with p.N34S mutation than in those without it (mean ± SD age: 32.0 ± 9.7 versus 39.1 ± 13.4 years; P = 0.004). No patient had any other mutation in the exon 3 of the SPINK1 gene, whereas one control had a heterozygous p.P55S mutation.

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. These findings suggest that p.N34S mutation lowers the threshold for occurrence of AP irrespective of the causative insult.