Risk of myocardial infarction associated with Gln/Arg 192 polymorphism in the human paraoxonase gene and diabetes mellitus. The REGICOR Investigators.
OBJECTIVE
There is increasing evidence that paraoxonase, an HDL-linked enzyme, exerts its effect by removing lipid-peroxidation products. We have conducted a case-control study in Gerona, Spain, to find out whether paraoxonase1 polymorphism at codon 192 (Q and R alleles) is associated with increased risk of coronary heart disease, and how diabetes mellitus, associated with high oxidative risk, influences such an association.


RESULTS
One hundred and fifty six consecutive myocardial infarction patients and 310 age- and sex-matched control subjects were studied. There were no differences in the distribution of genotype and allele frequencies between patients and controls. The odds ratios for diabetes and dyslipaemia in control and patients stratified by genotype group were compared. Whereas dyslipaemic status was significantly related to myocardial infarction in QQ homozygotes and R carriers, diabetes mellitus was significantly associated with myocardial infarction only in R-carrier subjects. In logistic regression analysis, diabetic R carriers demonstrated a more than two and a half-fold increase in myocardial infarction risk compared with non-diabetic R carriers (OR: 2.65, P<0.05).


CONCLUSIONS
These data indicate that the R allele of the paraoxonase1-192 polymorphism is not an independent risk factor for myocardial infarction in our population. However, the interaction between this polymorphism and diabetes mellitus leads to increased myocardial infarction risk in diabetic patients with the R allele.
Aubó
C
C
Lipids and Cardiovascular Epidemiology Unit, Institut Municipal d'Investigació Mèdica, IMIM, Barcelona, Spain.
Sentí
M
M
Marrugat
J
J
Tomás
M
M
Vila
J
J
Sala
J
J
Masiá
R
R
D000368:Aged; D001120:Arginine; D043303:Aryldialkylphosphatase; D016022:Case-Control Studies; D002784:Cholesterol / Q000097:blood; D003920:Diabetes Mellitus / Q000097:blood / Q000235:genetics; D003925:Diabetic Angiopathies / Q000097:blood / Q000235:genetics; D004950:Esterases / Q000235:genetics*; D005260:Female; D005838:Genotype; D005973:Glutamine; D006801:Humans; D006949:Hyperlipidemias / Q000235:genetics; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic
D005973:Glutamine; D001120:Arginine; D002784:Cholesterol; D004950:Esterases; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human