BACKGROUND: The cause of chronic pancreatitis (CP) remains unknown. However, oxidative stress might play a role since recent animal studies have demonstrated that oxygen-free radicals contribute to the pathogenesis of experimental pancreatitis. Human serum paraoxonase (PON1) is an antioxidant enzyme that protects against cellular damage from oxidative stress. Genetic variations resulting in variable activity rates of this enzyme, are of toxicological and physiological importance. AIM: We investigated whether genetic polymorphisms of the PON1 gene modify the risk for CP. MATERIALS AND METHODS: DNA samples were obtained from 236 adult CP patients of hereditary (n = 23), alcoholic (n = 137), or idiopathic (n = 76) origin. DNA from 113 healthy controls and from 93 alcoholic controls were analyzed for comparison. Patients and controls were all of Caucasian origin. Genetic polymorphisms (L55M and Q192R) in PON1 were determined by PCR, followed by restriction fragment length polymorphism analyses in all subjects. RESULTS: The frequencies of the PON1-55 alleles did not differ between CP patients and healthy controls. However, the PON1-192Q allele was significantly more common in idiopathic CP patients (OR : 1.5, 95% CI 1.02, 2.5) compared with healthy controls. CONCLUSIONS: These data suggest that the PON1-192Q allele, resulting in partly deficient antioxidant and detoxification activity of this enzyme, might be a risk factor for idiopathic CP in Caucasians.
BACKGROUND: The cause of chronic pancreatitis (CP) remains unknown. However, oxidative stress might play a role since recent animal studies have demonstrated that oxygen-free radicals contribute to the pathogenesis of experimental pancreatitis. Human serum paraoxonase (PON1) is an antioxidant enzyme that protects against cellular damage from oxidative stress. Genetic variations resulting in variable activity rates of this enzyme, are of toxicological and physiological importance. AIM: We investigated whether genetic polymorphisms of the PON1 gene modify the risk for CP. MATERIALS AND METHODS: DNA samples were obtained from 236 adult CP patients of hereditary (n = 23), alcoholic (n = 137), or idiopathic (n = 76) origin. DNA from 113 healthy controls and from 93 alcoholic controls were analyzed for comparison. Patients and controls were all of Caucasian origin. Genetic polymorphisms (L55M and Q192R) in PON1 were determined by PCR, followed by restriction fragment length polymorphism analyses in all subjects. RESULTS: The frequencies of the PON1-55 alleles did not differ between CP patients and healthy controls. However, the PON1-192Q allele was significantly more common in idiopathic CPpatients (OR : 1.5, 95% CI 1.02, 2.5) compared with healthy controls. CONCLUSIONS: These data suggest that the PON1-192Q allele, resulting in partly deficient antioxidant and detoxification activity of this enzyme, might be a risk factor for idiopathic CP in Caucasians.
Authors: D M Shih; L Gu; Y R Xia; M Navab; W F Li; S Hama; L W Castellani; C E Furlong; L G Costa; A M Fogelman; A J Lusis Journal: Nature Date: 1998-07-16 Impact factor: 49.962