OBJECTIVE: Tropical chronic pancreatitis (TCP) is a form of chronic pancreatitis seen in many tropical countries in young non-alcoholic subjects who are often malnourished. Nutritional deficiencies, either at the macro or micro level, and food toxins have been implicated in its causation, although there is no final proof to confirm this suggestion. Mutations of SPINK1 and CFTR genes have been proposed as disease modifiers, or as determinants of phenotypes. Mutations involving the calcium sensing receptor (CASR) have been suggested to increase the risk of chronic pancreatitis (CP), since high intracellular levels of calcium activate trypsinogen within the acinar cells. A combination of CASR and SPINK1 gene mutations has been proposed to predispose to idiopathic CP. The purpose of this study was to report on novel mutations in CASR, identified in TCP patients. MATERIAL AND METHODS: We screened our TCP patients for mutations in CASR and SPINK1 genes. In a cohort of 35 patients and an equivalent number of controls, genomic DNA was screened for mutations in CASR and SPINK1 by direct DNA sequencing. RESULTS: Four new mutations were found in the CASR gene. A combination of both SPINK1 (N34S) and CASR mutations was seen in 6% of the patients, while 22% harbored a single mutation. CONCLUSIONS: Our study suggests, for the first time, that CASR mutation may be a risk for TCP, and that this risk may be further increased if there is an associated SPINK1 mutation.
OBJECTIVE: Tropical chronic pancreatitis (TCP) is a form of chronic pancreatitis seen in many tropical countries in young non-alcoholic subjects who are often malnourished. Nutritional deficiencies, either at the macro or micro level, and food toxins have been implicated in its causation, although there is no final proof to confirm this suggestion. Mutations of SPINK1 and CFTR genes have been proposed as disease modifiers, or as determinants of phenotypes. Mutations involving the calcium sensing receptor (CASR) have been suggested to increase the risk of chronic pancreatitis (CP), since high intracellular levels of calcium activate trypsinogen within the acinar cells. A combination of CASR and SPINK1 gene mutations has been proposed to predispose to idiopathic CP. The purpose of this study was to report on novel mutations in CASR, identified in TCPpatients. MATERIAL AND METHODS: We screened our TCPpatients for mutations in CASR and SPINK1 genes. In a cohort of 35 patients and an equivalent number of controls, genomic DNA was screened for mutations in CASR and SPINK1 by direct DNA sequencing. RESULTS: Four new mutations were found in the CASR gene. A combination of both SPINK1 (N34S) and CASR mutations was seen in 6% of the patients, while 22% harbored a single mutation. CONCLUSIONS: Our study suggests, for the first time, that CASR mutation may be a risk for TCP, and that this risk may be further increased if there is an associated SPINK1 mutation.
Authors: Harrison X Bai; Matthew Giefer; Mohini Patel; Abrahim I Orabi; Sohail Z Husain Journal: J Clin Gastroenterol Date: 2012-09 Impact factor: 3.062
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Authors: Venkata Muddana; Janette Lamb; Julia-B Greer; Beth Elinoff; Robert H Hawes; Peter B Cotton; Michelle A Anderson; Randall E Brand; Adam Slivka; David C Whitcomb Journal: World J Gastroenterol Date: 2008-07-28 Impact factor: 5.742
Authors: Gregory A Coté; Dhiraj Yadav; Adam Slivka; Robert H Hawes; Michelle A Anderson; Frank R Burton; Randall E Brand; Peter A Banks; Michele D Lewis; James A Disario; Timothy B Gardner; Andres Gelrud; Stephen T Amann; John Baillie; Mary E Money; Michael O'Connell; David C Whitcomb; Stuart Sherman Journal: Clin Gastroenterol Hepatol Date: 2010-10-26 Impact factor: 11.382