Genetic testing is useful in the diagnosis of nonhereditary pancreatic conditions: CFTR GENE Part 2

Genetic testing

CFTR GENE Part 2CFTR is a large molecule with 1480 amino acids coded for by over 4400 nucleotides in 24 exons. Idiopathic chronic pancreatitis appears to be associated with some loss of CFTR function, which can be caused by many combinations of CFTR mutations. However, screening of the entire CFTR gene for mutations is difficult and very expensive, thereby limiting this approach to specialized research laboratories. Some commercial laboratories do offer clinical testing for a panel of mutations that are commonly associated with CF, but these panels may not include many of the ‘mild’ CFTR mutations that are associated with pancreatitis. Furthermore, since CFTR mutations are prevalent in the population, the identification of a polymorphism does not necessarily mean that it is the cause of pancreatitis. Nor does the presence of a CFTR polymorphism confer a high risk of pancreatitis in asymptomatic individuals. For example, the incidence of acute pancreatitis in the general population is 1 in 16,000, and the presence of the CFTR R117H genotype increases the risk 2.6-fold; thus, the overall risk of pancreatitis with this mutation is only 2.6 in 16,000, or 0.16%.

A major dilemma regarding genetic testing of patients with recurrent acute or chronic pancreatitis has already arisen. Cohn et al suggest that, at the present time, CFTR testing may be considered for individuals in whom pancreatitis appears to be the earliest manifestation of classic CF, or for young patients with pancreatitis and borderline sweat chloride values, so that individuals can be referred to CF centres or for genetic counselling. The situation is becoming more complicated, however, because the World Health Organization (WHO) is about to publish the Classification of Cystic Fibrosis and Related Disorders in the upcoming International Classification of Diseases (ICD-11). Dodge reported on the deliberations of several major European working groups during the Third International Symposium on Inherited Diseases of the Pancreas in Milan, Italy, on March 4 to 6, 2001; the conference proceedings have also been published. According to these guidelines, all patients with ‘chronic pancreatitis’ require testing for CFTR mutations, and the presence of even a single CFTR mutation identifies the patient as having a CF-associated disorder. This formulation raises a number of serious questions for which there are no answers, including: Which mutations must be considered? How can a single common CFTR mutation be diagnostic of CF-associated chronic pancreatitis? Is testing for CFTR mutations always warranted in patients with chronic pancreatitis? You will always find the required amount of at the pharmacy that will be happy to take best care of you by offering safe possibility to purchase the drugs you need without any need to get a prescription first or take any other extra steps.

The author believes that CFTR mutation analysis may play an important role in the future, but most of the work has been on severe CF-causing mutations in Caucasians, and large national studies have not been conducted for other ethnic populations.

This entry was posted in Pancreatic and tagged Cystic fibrosis transmembrane conductance regulator, Kazal type 1, Pancreatic secretory trypsin inhibitor, Serine protease inhibitor, Trypsin, Trypsinogen.