Genetic polymorphisms in alcohol-metabolizing enzymes and chronic pancreatitis.
OBJECTIVE
Alcohol misuse is now regarded as an important risk factor for development of chronic pancreatitis (CP). However, not every alcohol misuser develops CP and it therefore might be suggested that susceptibility could be further influenced by inter-individual variations in the activities of alcohol-metabolizing enzymes. Several genetic polymorphisms that may affect the activities of alcohol-metabolizing enzymes have been described. Therefore we determined whether polymorphisms in the genes for alcohol dehydrogenase 3 (ADH3) or cytochrome p450 2E1 (CYP2E1) predispose to the development of CP.


METHODS
DNA samples were obtained from 142 adult CP patients with hereditary (n = 21), alcoholic (n = 82) or idiopathic (n = 39) CP. DNA from 128 healthy controls and from 93 alcoholic controls was analysed for comparison. Patients and controls were all of Caucasian origin. Genetic polymorphisms in ADH3 and CYP2E1 were determined by PCR, followed by restriction-fragment-length-polymorphism analyses in all subjects.


RESULTS
The frequencies of ADH3 and CYP2E1 c1c2 genotypes did not differ between CP patients and alcoholic and healthy controls. However, a trend for a higher frequency of the CYP2E1 intron 6 D allele was demonstrated in patients with alcohol-induced CP, compared to that of healthy controls (OR = 3.03, 95%CI = 1.0-9.1) or alcoholic controls (OR = 2.76, 95%CI = 0.9-8.7).


CONCLUSIONS
These data suggest that the presence of the CYP2E1 intron 6 DD genotype might confer a higher risk of alcoholic CP.
Verlaan
Mariette
M
Department of Medicine, University Medical Centre St Radboud, Nijmegen, The Netherlands. m.verlaan@mdl.umcn.nl
Te Morsche
René H M
RH
Roelofs
Hennie M J
HM
Laheij
Robert J F
RJ
Jansen
Jan B M J
JB
Peters
Wilbert H M
WH
Drenth
Joost P H
JP
D000328:Adult; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D002908:Chronic Disease; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics*; D000431:Ethanol / Q000378:metabolism*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D019512:Pancreatitis, Alcoholic / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic
D000431:Ethanol; C420272:ADH1C protein, human; D000426:Alcohol Dehydrogenase; D019392:Cytochrome P-450 CYP2E1