Genetic testing is useful in the diagnosis of nonhereditary pancreatic conditions: SPINK1/PSTI GENE MUTATIONS Part 2

Gene-gene interactions

SPINK1/PSTI GENE MUTATIONS Part 2We have argued that SP1NK1 mutations act as disease promoters in that they lower the threshold for initiating pancreatitis or possibly worsen the severity of pancreatitis that is caused by other genetic or environmental factors. It has also been shown that the presence of PRSS1 and SP1NK1 mutations in the same person influences the phenotype. The author’s group and the Midwest Multicenter Pancreatic Study Group have collected a large database from kindreds of patients with hereditary pancreatitis; it currently includes 717 individuals, of whom 368 (51%) have confirmed pancreatitis. Unaffected individuals include relatives and spouses, who are essential for conducting genetic linkage studies, as well as 46 relatives who were found to be silent carriers for a PRSS1 mutation. From this data set, 39 persons were identified with PRSS1 mutations but without SP1NK1 mutations, and 22 with both PRSS1 and SP1NK1 mutations. The median age of disease onset was older for patients with mutations of PRSS1 alone than for patients with mutations in both genes. The possible interaction between SP1NK1 mutations and CFTR mutations may also be important. Because the SP1NK1 mutation is not sufficient to cause disease in most individuals (as already mentioned), the significantly earlier age of onset seen in persons with both PRSS1 and SP1NK1 mutations supports the concept that SP1NK1 acts as a disease modifier. You are always offered finest quality flovent inhaler at the pharmacy you can fully trust and enjoy being its customer. Why wouldn’t you, if it offers lowest prices in the industry and fast delivery that can be free for some orders?

Genetic testing for SPINK1 mutations

The discovery of this disease-associated mutation raises the question of when to undertake genetic testing. Identification of SP1NK1 mutations in patients with early chronic pancreatitis may provide important information about the cause of the disorder. On the other hand, because fewer than 1% of persons with heterozygous SP1NK1 mutation alone are at risk of developing pancreatitis, it is not worthwhile to test asymptomatic subjects. SP1NK1 mutations are associated with early onset of symptoms; therefore, testing is unlikely to be fruitful in patients who develop pancreatitis after the age of 20 years.

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.