A abnormal CFTR allele and a SPINK1 mutation increase the risk of pancreatic disease in individuals with pancreas divisum

Pancreas divisum (PD) has been described as a risk factor for recurrent pancreatitis or chronic pancreatitis. There is still a controversy of the role of PD in developing pancreatic disease. The aim of this study was to elucidate genetic and environmental risk factors in patients with PD. Methods: In this case control study 63 patients (female29; male 34) with recurrent acute or chronic pancreatitis without any other known reason except for PD, 18 patients with an asymptomatic PD, and 240 healthy controls were enrolled. Patients were screened for 36 alterations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, the N34S mutation of the serine protease inhibitor, Kazal type 1 (SPINK1) gene, and the A16V, K23R, N29I, R122C, R122H mutations of the cationic trypsinogen (PRSS1) gene. A detailed history including alcohol and smoking was recorded. Results: In the symptomatic PD group 43 (68%) smoked compared to 12 (66%) in the asymptomatic PD group (n.s.). Alcohol intake in the symtomatic PD was 297±110 gr./week versus 147±57 gr./week (n.s.). 16/63 (25%) in the symptomatic PD, 3/18 (16%) in the asymptomatic PD, and 31/240 (12%) in controls showed a abnormal CFTR allele (p<0.02). 6/63 (7.9%), 1/18 (5.6%), and 3/240 (1.3%) were heterozygote for N34S (p<0.02). One patient was compound heterozygote for N34S and the R117H CFTR variation. The presence of a abnormal CFTR allele indicate a RR of 1.9 [95% CI, 1.2–3.4] and the N34S mutation a RR of 6.3 [95% CI, 1.5–25.9] for pancreatitis. 44 patients underwent endoscopic minor papillary spincterotomy followed in 17 patients by surgical resection. Eight from these 17 patients (47%) had a CFTR alteration compared to 8/46 (17%) without surgery (RR 2.61 [1.22–5.61], p=0.03). Conclusion: The presence of a abnormal CFTR allele and of the SPINK1 mutation N34S increase the risk of symptomatic pancreatic disease in persons with PD and the presence of a CFTR variation is a negative predictor for success of endoscopic treatment. Although this observation may explain why a subgroup of PD patients develop pancreatic disease, the majority of patients with symptomatic PD constitute a heterogenous group.

Keywords: Endoskopische Therapie, Genetik, Pankreas