Alcoholic pancreatitis and polymorphisms of the variable length polythymidine tract in the cystic fibrosis gene

Background: The observation that only a minority of alcoholics develops cli nical pancreatic disease has led to a search for a predisposing factor to t he disease. One possible predisposing factor is mutation of the cystic fibr osis transmembrane conductance regulator (CFTR) gene as cystic fibrosis lea ds to pancreatic injury. We have recently demonstrated that 15 common CFTR mutations are not found in patients with alcoholic pancreatitis. Another co mmon polymorphism of the CFTR gene has recently been implicated in the path ogenesis of idiopathic chronic pancreatitis, the 5T variant of the variable length polythymidine tract in intron 8 (the normal genotypes are 7T and 9T ). The 5T variant inhibits transcription of exon 9 resulting in a CFTR prot ein lacking chloride channel activity. The aim of this study was to determi ne whether the 5T variant is associated with alcoholic pancreatitis. Method s: Fifty-two patients with alcoholic pancreatitis were identified using sta ndardized diagnostic criteria. Fifty alcoholics without pancreatitis were a lso studied as controls. Genomic DNA was extracted from peripheral blood le ukocytes and the polythymidine tract of intron 8 was amplified by nested po lymerase chain reaction using established primers. The polymerase chain rea ction products were digested with MseI, separated by electrophoresis on 15% polyacrylamide gels and genotypes assigned by comparison with known positi ve controls. Results: The 5T allele was found in only two patients with alc oholic pancreatitis (3.9% of the index group; 95% confidence intervals 0-10 %) and in seven alcoholic controls. Allele frequencies for 5T, 7T, and 9T i n patients with alcoholic pancreatitis were 1.9%, 85.6%, and 12.5%, respect ively. These did not differ from the allele frequencies in alcoholic: contr ols (7%, 79%, and 14% for 5T, 7T, and 9T, respectively). Conclusion: The 5T allele was not associated with alcoholic pancreatitis. Individual suscepti bility to this disease remains unexplained.