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BY OUR PHARMA CORRESPONDENT
17 September,2005: Indian scientists have identified the link between SPINK1 gene and
prancraetitis.
Scientists from Hyderabad-based Centre for Cellular and Molecular Biology (CCMB) have found the role of SPINK1 (serine protease inhibitor, kazal type 1; SPINK1) mutations in chronic pancreatitis.
Pancreatisis symptom
Pancreatitis is inflammation of the
pancreas. Insulin and glucagon
production is managed by the Pancreas.
The most obvious symptom of
pancreatitis is upper abdominal pain.
Abdominal distension is another
pancreatitis symptom as fluid behind
the abdominal organs pushes the
abdominal organs forward.
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A team of scientists from Hyderabad-based Centre for Cellular and Molecular Biology (CCMB) have found the role of SPINK1 (serine protease inhibitor, kazal type 1; SPINK1) mutations trough undertaking a study on a large group of patients with hereditary pancreatitis (HP) and non-hereditary pancreatitis, alcoholic chronic pancreatitis (ACP) to determine if PRSS1 and SPINK1 mutations are associated with chronic pancreatitis in India.
In total, 198 patients (120 ICP, 41 ACP and 31 HP) and 24 unaffected relatives from HP families participated in the study. The Institutional Ethics Committee approved the study following the guidelines for research on human subjects. The samples were analysed at CCMB. Genomic DNA was isolated from leucocytes following standard protocols and initially all samples were screened for commonly reported mutations in PRSS1 gene. Subsequently, both PRSS1 and SPINK1 genes were sequenced in all the patients and controlled to screen for any novel mutations in these patients.
Mutations in the cationic trypsinogen (protease serine, 1 (trypsin 1); PRSS1) gene are known to be causally associated with recurrent acute and
chronic pancreatitis. The team investigated whether mutations in the PRSS1 gene are associated with hereditary and non-hereditary pancreatitis. As a modifier role has been proposed for trypsin inhibitor (serine protease inhibitor, kazal type 1; SPINK 1) mutations, its role was also analysed in these patients.
The team found for the first time, the absence of PRSS1 mutations in Indian patients with chronic pancreatitis of different aetiologies, which confirm observations made previously in Indian TCP patients. This is most likely related to their genetic makeup as no other study from abroad has reported absence of PRSS1 mutations in hereditary as well as in non-hereditary chronic pancreatitis patients.
Surprisingly, a simultaneous strong association with SPINK1 mutations, particularly N34S mutation was identified in all types of pancreatitis, albeit the strength of association differed.
Interaction with other factors, such as environmental and nutritional influences, may also play an important role and explain the variability. The study also suggested the possibility of phenomenon of racial specificity since the background prevalence of N34S SPINK1 mutation was varying from the earlier reported frequency from different populations in different countries.
CCMB study finding strongly suggests that irrespective of its aetiology, established mutations in PRSS1 are not a common cause of chronic pancreatitis in the Indian population. However, SPINK1 mutations were found to be strongly associated with all types of chronic pancreatitis. Most patients with a SPINK1 variation had N34S mutation and the prevalence was significantly higher in HP patients (with 73 per cent) compared with ICP patients (32.5 per cent) and ACP patients (26.8 per cent).
The genetic basis of chronic pancreatitis in India has rarely been explored and only a few studies had focused only on tropical calcific pancreatitis.
The findings of the recent study can pave way towards genetic screening for susceptibility for development of the disease. It is estimated that 1.5 per cent to 4 per cent of our population can be affected by chronic pancreatitis in India and is usually seen in the people who are in second and third decades.
BY OUR PHARMA CORRESPONDENT More
on Pancreatitis symptoms here |
