The Most Important Candidate Genes For Pancreatic Stone Formation

Main Category: GastroIntestinal / Gastroenterology
Article Date: 14 Nov 2007 - 6:00 PDT

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Stone formation is an important feature of chronic pancreatitis, especially tropical calcific pancreatitis (TCP), where the stones are large in size, highly irregular in shape and cause enormous tissue destruction. The exact mechanism of stone formation is not well-understood. It is very important to understand the initial event so that stone formation can be controlled before it causes obstruction and damage to the pancreatic tissue. One such study was recently reported in the November 28 issue of the World Journal of Gastroenterology because of its significance in pancreatic diseases.

In an attempt to understand the initiating event in stone formation in chronic pancreatitis, Dr. Chandak and his group initiated this study. Protein plug formation is an important primary event in the final stone formation and hence some proteins must be increased in their concentration in the pancreatic juice. Lithostathine (encoded by reg1 gene) has been isolated as a major protein component from stones of alcoholic chronic pancreatitis patients, and has been found to be 2 to 3 times less abundant in the pancreatic juice of chronic pancreatitis patients than in controls. Although the exact function of reg1 protein is not clear, it has been proposed to regulate the process of stone formation.

The team proposed that mutations in the promoter region of reg1 could lead to altered levels of the protein, or that the gene variants could predispose the reg1 protein to increased cleavage by trypsin and form fibrils that may precipitate and obstruct the duct by forming protein plugs and calculi. The interaction between pancreatic inflammation and stone formation in chronic pancreatitis is also not well understood; this study also investigated the interaction between the reg1 gene and the established susceptibility genes for TCP, such as pancreatic secretory trypsin inhibitor and cathepsin B (encoded by SPINK1 and CTSB respectively).

On testing the hypothesis in a large cohort of ethnically matched TCP patients and normal individuals, Dr. Chandak and his group discovered that mutations in reg1, including those in the regulatory region either independently or in the presence of known mutations in SPINK1 and/or CTSB, might not be a cause of stone formation in TCP patients. This opens up scope for further research on alternative mechanisms, such as calcium signaling and regulation in stone formation in chronic pancreatitis.

The observations made by this study thus contribute significantly by ruling out the role of one of the most important candidate genes for pancreatic stone formation.

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Reference: Mahurkar S, Bhaskar S, Reddy DN, Rao GV, Chandak GR. Comprehensive screening for reg1 gene rules out association with tropical calcific pancreatitis. World J Gastroenterol 2007; 13(44): 5938-5943
http://www.wjgnet.com/1007-9327/13/5938.asp

Correspondence to:
Giriraj Ratan Chandak, MD,
Centre for Cellular and Molecular Biology,
Uppal Road, Hyderabad
500 007, India.
http://www.ccmb.res.in

About World Journal of Gastroenterology

World Journal of Gastroenterology (WJG), a leading international journal in gastroenterology and hepatology, has established a reputation for publishing first class research on esophageal cancer, gastric cancer, liver cancer, viral hepatitis, colorectal cancer, and H pylori infection for providing a forum for both clinicians and scientists. WJG has been indexed and abstracted in Current Contents/Clinical Medicine, Science Citation Index Expanded (also known as SciSearch) and Journal Citation Reports/Science Edition, Index Medicus, MEDLINE and PubMed, Chemical Abstracts, EMBASE/Excerpta Medica, Abstracts Journals, Nature Clinical Practice Gastroenterology and Hepatology, CAB Abstracts and Global Health. ISI JCR 2003-2000 IF: 3.318, 2.532, 1.445 and 0.993. WJG is a weekly journal published by The WJG Press. The publication dates are the 7th, 14th, 21st, and 28th day of every month. The WJG is supported by The National Natural Science Foundation of China, No. 30224801 and No. 30424812, and was founded with the name of China National Journal of New Gastroenterology on October 1, 1995, and renamed WJG on January 25, 1998.

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Source:
You-De Chang
World Journal of Gastroenterology

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