Carboxylester lipase gene polymorphism as a risk of alcohol-induced pancreatitis

Objectives: Alcohol abuse causes pancreatic damage in humans. However, only 5% of alcoholic patients have a clinical manifestation of pancreatitis, and the genetic predisposition of alcohol-associated pancreatitis remains elusive. Nonoxidative metabolites of ethanol, fatty acid ethyl esters (FAEEs), might play an important role in pancreatic damage. Carboxylester lipase (CEL) has been known to catalyze FAEE synthesis from fatty acids and ethanol. Methods: The variable number of tandem repeat ( VNTR) polymorphism in the coding region of the CEL gene was studied in patients with alcoholic pancreatitis (n = 100), in alcoholics without pancreatitis ( n = 52), in patients with nonalcoholic pancreatitis ( n = 50), in hyperlipidemia patients ( n = 96), and control subjects ( n = 435). Results: The frequency of the NN-type (wild-type) gene was significantly decreased in patients with alcoholic pancreatitis than in other groups. The frequency of subjects who had the L allele in patients with alcoholic pancreatitis was significantly higher than in other groups. The distribution of the CEL gene polymorphism was not different among the control subjects, alcoholics without pancreatitis, patients with nonalcoholic pancreatitis, and patients with hyperlipidemia. Conclusions: The CEL gene polymorphism, especially an increase in the frequency of the L allele, was found to be associated with alcohol-induced pancreatitis.