Glutathione S-transferase Mu null genotype affords protection against alcohol induced chronic pancreatitis.
Glutathione S-transferases (GSTs) play critical roles in providing protection against electrophiles and products of oxidative stress, by catalysing the formation of glutathione conjugates and by eliminating peroxides. Most extensively studied are four main families of human cytosolic GST: GSTAlpha(A), GSTMu(M), GSTPi(P) and GSTTheta(T). Absence of GSTM1 or GSTT1 can be attributed to absence of the GSTM1 or GSTT1 gene products (null genotype) in approximately 50% and 20% of the Caucasian population, respectively. We investigated whether polymorphisms in the GSTM1, GSTT1 and GSTP1 genes modified the risk for chronic pancreatitis (CP). DNA samples were obtained from 142 adult CP patients with alcoholic (n = 79), hereditary (n = 21) or idiopathic (n = 42) origin. DNA from 204 healthy controls and from 57 alcoholic controls was analysed for comparison. Patients and controls were all of Caucasian origin. Genetic polymorphisms in GSTs were determined by PCR, eventually followed by restriction-fragment-length-polymorphism analyses in all subjects. The rates of GSTT1 and GSTP1 genotypes did not differ between CP patients and healthy controls. However, GSTM1 null genotypes were significantly less common in alcoholic CP patients (OR = 0.56, 95% CI: 0.33-0.95) as compared to healthy controls and to alcoholic controls (OR = 0.52, 95% CI: 0.26-1.04). Age- and sex-adjustment bolstered our finding (adjusted OR = 0.48, 95% CI: 0.26-0.89). The frequency of the GSTM1 null genotype is significantly lower in alcoholic CP patients, especially young female. This suggests that GSTM1 null alcohol users, particularly young female, are less susceptible to CP.
Verlaan
Mariette
M
Department of Medicine, Division of Gastroenterology and Hepatology, University Medical Centre, St. Radboud, PO Box 9101, 6500 HB Nijmegen, The Netherlands. M.Verlaan@gastro.azn.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; D000367:Age Factors; D000428:Alcohol Drinking; D002908:Chronic Disease; D004247:DNA / Q000235:genetics; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D010195:Pancreatitis / Q000139:chemically induced*; D010545:Peroxides / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic
D010545:Peroxides; D004247:DNA; C413545:glutathione S-transferase T1; D005982:Glutathione Transferase