Surgery
Indian scientists identify second pancreatitis gene - cathepsin B
By IANS
Apr 8, 2006 - 5:34:00 AM

Indian scientists have discovered a second candidate gene - cathepsin B - responsible for the fatal tropical calcific pancreatitis disease that leads to a gradual destruction of the pancreas.

A chronic disease that leads to progressive destruction of pancreas and a painful death, pancreatitis can strike people in tropical countries, including India, and in the west.

The gene was identified by experts of two premier Hyderabad-based scientific institutions - the Centre for Cellular and Molecular Biology (CCMB) and the Asian Institute of Gastroenetrology (AIG).

CCMB chief G.R. Chandak and D. Nageshwar Reddy of AIG told reporters in Hyderabad Friday that their extensive study found two different genes that caused pancreatitis.

Since the experts started collaborative research on the subject, this is the second candidate gene they have found responsible for causing the chronic pancreatitis.

Earlier, they had identified the involvement of the mutation of another gene - SPINK1.

"SPINK1 produces protein trypsin, which normally works as an inhibitor inside the pancreas. But mutation in SPINK1 gene can reduce the inhibitory function of trypsin, which becomes active inside pancreas and starts digesting the pancreas itself," Chandak said.

However, they found that the mutation of SPINK1 gene was not present in all patients of chronic pancreatitis and it raised the possibility of other genes also causing the same disease. Further research led to the discovery of another gene - cathepsin B - that causes the same disease.

According to the study, which was carried by international medical journal GUT in its online edition, the mutation of cathepsin B works like a trigger for trypsinogen to become active prematurely inside the pancreas and thus damage the pancreas.

Chandak said that even though these two genes work from different pathways, the next task before his team was to find whether there was any link between the two and its role.

In case of pancreatitis in the west, the disease is caused by the mutation of another gene - cationic trypsinogen - and this mutation is not found among the populations of tropical countries.

"This underlines the need for conducting separate research on the genetic basis of different diseases that are typical to our countries," Reddy said.

The study covered 306 patients and 330 healthy people, almost half of them from the state of Kerala, where the disease is reportedly rampant.

CCMB director Lalji Singh described the development as immensely significant. He said: "No one in the past had found the mutation of this gene. This is the first time in the world that it has been identified".

"If we put together SPINK1, the first mutation gene and the second mutation gene, it will be possible in the future to predict via screening a newborn baby's propensity for pancreatitis.

"On the basis of the prediction, a clinic can counsel on diet and lifestyles. It will be even possible to prevent the disease," he said.

Pancreas, the second most important organ in the human body after the heart, plays a major role in digestion of food and regulation of blood glucose mechanism in the body.

"Whenever pancreas becomes abnormal or develop chronic pacnreatitis, then the patient will develop diabetes mellitus because the glucose cannot be properly regulated and insulin is not secreted. Further degeneration leads to cancer of pancreas and it proves fatal," said Reddy.

The disease is also one of the major contributing factors in causing diabetes, the incidence of which is very high among Indians.

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