Scientists from the Centre for Cellular and Molecular Biology (CCMB) and the Asian Institute of Gastroenterology (AIG), along with a group of scientists from Germany, Japan and Europe, have discovered a new gene-association with the early onset of chronic pancreatitis.
The team has found that chronic pancreatitis among Indians has a genetic basis which is different from the case of other Asians and Europeans. Announcing the breakthrough, which is being published in the international journal, ‘Nature Genetics’, on Monday, CCMB director Dr Ch Mohan Rao, project group leader Dr GR Chandak and team members AIG managing director Dr D Nageshwar Reddy and chief of surgical gasteroenterology Dr GV Rao said they established the genetic basis of tropical calcific pancreatitis (TCP) and identified the involvement of Spink1 gene, which produces a protein that inhibits the active trypsin inside the pancreas and cathepsin B gene that regulates activation of trypsinogens in the pancreas. These discoveries have led to the inclusion of TCP in the Online Mendelian Inheritance in Man as a genetic disease.
Dr Chandak said that it was found that the involvement of this gene was different from the gene (cationic and anionic trypsinogen) implicated in other types of chronic pancreatitis in western populations and they, therefore, proposed that in India chronic pancreatitis had a different genetic basis and the results of research conducted abroad cannot be extrapolated for Indian population.
He said they investigated several genes, including Chymotrypsin-C and CFTR and identified novel mutations that are different from those prevalent among Europeans. It was found that not only the genetic spectrum but also the mutational spectrum of TCP or chronic pancreatitis in India is different.
Dr Chandak said the pathway of development of chronic pancreatitis among Indians is different and hence the genetic testing for risk prediction would also be different. Although the mutation is present in only 2 percent of the patents, it drives home the point that the pathway of trypsinogen activation and deactivation is important overall and assumes immense importance since Indian patients do not carry cationic trypsinogen mutations. Dr Nageshwar Reddy said that since this mutation is also predictive of the early onset of pancreatitis, early detection and modification of the course of the disease would be helpful. The study has the potential for the development of a genetic screening test for susceptibility to chronic pancreatitis among the Indian population at an early age.
“In the southern part of the country, incidents of pancreatitis are very high, especially in Karnataka, Kerala, Odisha and Andhra Pradesh. In some villages in Kerala, one in a thousand has pancreatitis. In western countries the main cause of pancreatitis is alcohol whereas in India it is genetic mutation,” Dr Reddy said.
About 300 patients’ databases are being sequenced by the team and the work would be completed within two years, he said.
The breakthrough has come after 13 years of research involving scientists and clinicians from 25 countries.