Schneider Alexander, Suman Amitabh, Rossi Livio, Barmada M Michael, Beglinger Christoph, Parvin Shahana, Sattar Soheli, Ali Liaquat, Khan A K Azad, Gyr Niklaus, Whitcomb David C
Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
Gastroenterology. 2002 Oct;123(4):1026-30. doi: 10.1053/gast.2002.36059.
BACKGROUND & AIMS: 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.
热带胰腺炎，包括热带钙化性胰腺炎和纤维钙化性胰腺糖尿病，在亚洲和非洲部分地区呈地方性流行。在一项初步研究中，我们在孟加拉国8例纤维钙化性胰腺糖尿病患者中的6例发现了丝氨酸蛋白酶抑制剂Kazal型1（SPINK1）突变。我们对孟加拉国包括非胰岛素依赖型糖尿病在内的胰腺疾病患者进行了更广泛的调查。
对来自孟加拉国的纤维钙化性胰腺糖尿病患者（22例）、热带钙化性胰腺炎患者（15例）、非胰岛素依赖型糖尿病患者（43例）以及对照者（76例）进行研究。提取DNA，并对所有患者和50例对照者的SPINK1基因进行测序。另外26例对照者对第3外显子进行测序。
SPINK1 N34S突变出现在76例对照者中的1例（1.3%）、22例纤维钙化性胰腺糖尿病患者中的12例（55%；优势比，83；P<0.00001）、15例热带钙化性胰腺炎患者中的3例（20%；优势比，11.2；P=0.04）以及43例非胰岛素依赖型糖尿病患者中的6例（14%；优势比，11.9；P=0.009）。P55S存在于76例对照者中的2例（3%）以及22例纤维钙化性胰腺糖尿病患者中的1例（5%；P无显著性差异）。在15例热带钙化性胰腺炎患者中的1例发现了一种新的Y54H（160T>C）突变。
在孟加拉国，SPINK1 N34S突变增加了几种胰腺疾病的发病风险，包括纤维钙化性胰腺糖尿病、热带钙化性胰腺炎和非胰岛素依赖型糖尿病。
