Paraoxonase 1 gene polymorphisms in angiographically assessed coronary artery disease: evidence for gender interaction among Brazilians

Background: Paraoxonases (PON) are members of an enzyme family involved in preventing low-density lipoprotein oxidation and therefore protecting against atherosclerotic plaque formation. Methods: We studied the Met55Leu and GIn192Arg PON1 polymorphisms in 712 patients (437 Caucasian- and 275 African-Brazilians) who underwent coronary angiography. Results: Among Caucasian-Brazilians, the homozygous 55LeuLeu frequency was higher among patients with significant coronary artery disease (CAD, obstructive lesions >= 50%) than among lesion-free controls (51% vs. 30.3%; p=0.022) in females, but not in males. The GIn192Arg PON1 polymorphism was not associated with CAD, although 192GlnGln homozygotes presented lower high-density lipoprotein (HDL)-cholesterol (p=0.035) and higher triglyceride (p=0.012) levels than 192Arg allele carriers among Caucasian-Brazilian males, but not females. No other lipid-genotype association was detected. Multivariate logistic regression corrected for classic CAD risk factors shows that 55LeuLeu PON1 homozygotes were at increased CAD risk (odds ratio OR=2.852; p=0.003) and that this genotype interacted with gender in its association with CAD risk (OR=0.290; p=0.006) among Caucasian-Brazilians. Conclusions: This report shows that the 55LeuLeu PON1 genotype increases CAD risk among female Caucasian-Brazilians, irrespective of other CAD risk factors. In addition, 192GlnGln PON1 homozygotes show higher triglyceride and lower HDL-cholesterol levels in male Caucasian-Brazilians. No associations were detected among African-Brazilians.