SPINK1/PSTI mutations are associated with tropical pancreatitis and type II diabetes mellitus in Bangladesh.

Tropical pancreatitis, including tropical calcific pancreatitis and fibrocalculous pancreatic diabetes, is endemic in parts of Asia and Africa. In a preliminary study, we found serine protease inhibitor, Kazal type 1 (SPINK1) mutations in 6 of 8 patients with fibrocalculous pancreatic diabetes in Bangladesh. A more extensive investigation of patients with pancreatic diseases in Bangladesh, including non-insulin-dependent diabetes mellitus, was undertaken. Patients with fibrocalculous pancreatic diabetes (n = 22), tropical calcific pancreatitis (n = 15), and non-insulin-dependent diabetes mellitus (n = 43) and controls (n = 76) from Bangladesh were studied. DNA was extracted, and the SPINK1 gene was sequenced in all patients and 50 controls. Exon 3 was sequenced in an additional 26 controls. SPINK1 N34S mutations appeared in 1 of 76 controls (1.3%), 12 of 22 patients with fibrocalculous pancreatic diabetes (55%; odds ratio, 83; P < 0.00001), 3 of 15 with tropical calcific pancreatitis (20%; odds ratio, 11.2; P = 0.04), and 6 of 43 with non-insulin-dependent diabetes mellitus (14%; odds ratio, 11.9; P = 0.009). P55S was present in 2 of 76 controls (3%) and in 1 of 22 patients with fibrocalculous pancreatic diabetes (5%; P = not significant). A novel Y54H (160T>C) mutation was identified in 1 of 15 tropical calcific pancreatitis patients. In Bangladesh, the SPINK1 N34S mutation increases the risk of several forms of pancreatic disease, including fibrocalculous pancreatic diabetes, tropical calcific pancreatitis, and non-insulin-dependent diabetes mellitus.