Interaction between smoking and PON2 Ser311Cys polymorphism as a determinant of the risk of myocardial infarction.
BACKGROUND
Increased oxidative stress is thought to play a role in the pathogenesis of the atherothrombotic process. Paraoxonases (PONs) are closely related antioxidant enzymes encoded by clustered genes on chromosome 7q. We evaluated three PON polymorphisms (PON1 Leu55Met and Gln192Arg; PON2 Ser311Cys) as possible risk factors for coronary atherosclerotic disease (CAD) and/or its main thrombotic complication, myocardial infarction (MI).


METHODS
We studied 890 subjects with angiographic documentation of coronary vessels (272=CAD-free; 618=CAD). In the CAD group, 341 subjects had a previous MI.


RESULTS
Frequencies of various genotypes were not significantly different between CAD-free subjects and the entire CAD population. In the latter group, there were more carriers of the PON2 311Cys variation among those who had suffered a MI than among those who had not (P<0.01 by chi2). The adjusted OR for MI among PON2 311Cys carriers was 1.5 (95%CI, 1.03-2.19). A gene-environmental interaction was found between PON2 Ser311Cys and smoking. Smoking by itself was associated with an increased MI risk. Among smokers, however, the MI risk was related to PON2 genotype: Cys/Cys homozygotes (OR=5.3; 95%CI, 1.7-16.4) and Ser/Cys heterozygotes (OR=2.1; 95%CI, 1.3-3.6) were at greater risk than Ser/Ser subjects (OR=1.2; 95%CI, 0.8-1.8). The PON2 polymorphism did not influence the MI risk among nonsmokers.


CONCLUSIONS
In CAD subjects, a proportion of the risk of MI may be influenced by the interaction between smoking and a polymorphism in the antioxidant enzyme PON2.
Martinelli
N
N
Department of Clinical and Experimental Medicine, University of Verona, Verona, Italy.
Girelli
D
D
Olivieri
O
O
Stranieri
C
C
Trabetti
E
E
Pizzolo
F
F
Friso
S
S
Tenuti
I
I
Cheng
S
S
Grow
M A
MA
Pignatti
P F
PF
Corrocher
R
R
D043303:Aryldialkylphosphatase / Q000235:genetics*; D003324:Coronary Artery Disease / Q000097:blood / Q000201:enzymology / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000201:enzymology / Q000235:genetics*; D018384:Oxidative Stress / Q000502:physiology; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects* / Q000235:genetics
D008315:Malondialdehyde; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human; C468411:PON2 protein, human