The most important candidate genes for pancreatic stone formation

Nov 13, 2007

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.

Source: World Journal of Gastroenterology

Explore further: A new era for genetic interpretation

Related Stories

Defusing bombs by color

18 minutes ago

This March, Cambodia held its first national-level science festival at the Royal University of Phnom Penh, attracting over 10,000 young students to the science booths over the course of three days. At one ...

Mars rover's ChemCam instrument gets sharper vision

19 minutes ago

NASA's Mars Curiosity Rover's "ChemCam" instrument just got a major capability fix, as Los Alamos National Laboratory scientists uploaded a software repair for the auto-focus system on the instrument.

How we discovered the three revolutions of American pop

8 minutes ago

Dr Matthias Mauch discusses his recent scientific analysis of the "fossil record" of the Billboard charts prompted widespread attention, particularly the findings about the three musical "revolutions" that shaped the musical la ...

Detecting and blocking leaky Android apps

21 minutes ago

Nine times out of ten, that Android app is connecting to multiple internet destinations without your knowledge, more than half of them require access to the sensitive, personal information on your mobile device in order to ...

Recommended for you

A new era for genetic interpretation

10 minutes ago

Millions of genetic variants have been discovered over the last 25 years, but interpreting the clinical impact of the differences in a person's genome remains a major bottleneck in genomic medicine. In a paper published in ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.