Paraoxonase 1-192Q allele is a risk factor for idiopathic chronic pancreatitis.
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.


OBJECTIVE
We investigated whether genetic polymorphisms of the PON1 gene modify the risk for CP.


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.
Verlaan
Mariette
M
Department of Medicine, Division of Gastroenterology and Hepatology, Radboud University Medical Centre, Nijmegen, The Netherlands.
Harbers
Erik G A
EG
Pap
Akos
A
Jansen
Jan B M J
JB
Peters
Wilbert H M
WH
Drenth
Joost P H
JP
D000328:Adult; D000483:Alleles; D000975:Antioxidants / Q000378:metabolism; D043303:Aryldialkylphosphatase / Q000235:genetics*; D002908:Chronic Disease; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008297:Male; D008875:Middle Aged; D010195:Pancreatitis / Q000201:enzymology / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D012307:Risk Factors
D000975:Antioxidants; D043303:Aryldialkylphosphatase