OBJECTIVES: Chronic pancreatitis (CP) is associated with alcohol abuse, smoking and other dietary or environmental factors. UDP-glucuronosyltransferases (UGTs) are phase II detoxifying enzymes responsible for glucuronidation of various exogenous and endogenous compounds. Genetic variations, resulting in variable rates of glucuronidation, are of toxicological and physiological importance and are frequently associated with diseases. Recently, a genetic polymorphism in UGT1A7 was possibly associated with an increased risk for CP. We investigated whether polymorphisms in the genes for UGT1A1, UGT1A6 and UGT1A8 modified the risk for CP. METHODS: DNA samples were obtained from 258 adult CP patients with alcoholic (n = 153), hereditary (n = 25) or idiopathic (n = 80) origin. DNA from 140 healthy controls was analyzed for comparison. Patients and controls were all of Caucasian origin. Genetic polymorphisms in UGTs were determined by PCR, eventually followed by restriction-fragment-length-polymorphism analyses in all subjects. RESULTS: The distribution of the various alleles of UGT1A1, UGT1A6 and UGT1A8 did not differ between CP patients and healthy controls. CONCLUSION: These data suggest that genetic polymorphisms in UGT1A1, UGT1A6 and in UGT1A8 do not predispose to the development of CP in Caucasians.
OBJECTIVES:Chronic pancreatitis (CP) is associated with alcohol abuse, smoking and other dietary or environmental factors. UDP-glucuronosyltransferases (UGTs) are phase II detoxifying enzymes responsible for glucuronidation of various exogenous and endogenous compounds. Genetic variations, resulting in variable rates of glucuronidation, are of toxicological and physiological importance and are frequently associated with diseases. Recently, a genetic polymorphism in UGT1A7 was possibly associated with an increased risk for CP. We investigated whether polymorphisms in the genes for UGT1A1, UGT1A6 and UGT1A8 modified the risk for CP. METHODS: DNA samples were obtained from 258 adult CP patients with alcoholic (n = 153), hereditary (n = 25) or idiopathic (n = 80) origin. DNA from 140 healthy controls was analyzed for comparison. Patients and controls were all of Caucasian origin. Genetic polymorphisms in UGTs were determined by PCR, eventually followed by restriction-fragment-length-polymorphism analyses in all subjects. RESULTS: The distribution of the various alleles of UGT1A1, UGT1A6 and UGT1A8 did not differ between CP patients and healthy controls. CONCLUSION: These data suggest that genetic polymorphisms in UGT1A1, UGT1A6 and in UGT1A8 do not predispose to the development of CP in Caucasians.
Authors: Martijn G H van Oijen; Sylvie Huybers; Wilbert H M Peters; Joost P H Drenth; Robert J F Laheij; Freek W A Verheugt; Jan B M J Jansen Journal: Br J Clin Pharmacol Date: 2005-12 Impact factor: 4.335