PARAOXONASE PON1 POLYMORPHISM LEU-MET54 IS ASSOCIATED WITH CAROTID ATHEROSELEROSIS - RESULTS OF THE AUSTRIAN STROKE PREVENTION STUDY

Background and Purpose-Genetic polymorphism at the paraoxonase locus i s associated with serum concentration and activity of paraoxonase and with increased risk for coronary heart disease. Two frequent polymorph isms present at the paraoxonase gene are the methionine (M allele) leu cine (L allele) interchange at position 54 and the arginine (B allele) glutamine (A allele) interchange at position 191. This is the first s tudy to determine the effect of these polymorphisms on carotid atheros clerosis. Methods-The paraoxonase genotypes at positions 54 and 191 of 316 randomly selected individuals aged 44 to 75 years were determined by polymerase chain reaction-based restriction enzyme digestion. Caro tid atherosclerosis was assessed by color-coded Duplex scanning and wa s graded on a 5-point scale ranging from 0 (normal) to 5 (complete lum inal obstruction). Results-The LL, LM, and MM genotypes at position 54 were noted in 137 (43.4%), 132 (41.8%), and 47 (14.9%) subjects; the AA, AB, and BE genotypes at position 191 occurred in 172 (54.4%), 124 (39.2%), and 20 (6.3%) individuals. The LL genotype was significantly associated with the presence and severity of carotid disease (P=0.022) , whereas the 191 polymorphism had no effect. Logistic regression anal ysis with age and sex forced into the model demonstrated plasma fibrin ogen (odds ratio [OR], 1.005 per mg/dL), LDL cholesterol (OR, 1.01 per mg/dL),cardiac disease (OR, 1.75), and the paraoxonase LL genotype to be significant predictors of carotid atherosclerosis. The ORs for the associations with age and sex were 1.09 (P=0.0003) and 1.66 (P=0.052) per year. Conclusions-These data suggest that the paraoxonase LL geno type may represent a genetic risk factor for carotid atherosclerosis.