Association of paraoxonase-1 M55L genotype and alcohol consumption with coronary atherosclerosis: the Helsinki Sudden Death Study.

High-density lipoprotein (HDL) level is inversely correlated with coronary heart disease risk. Paraoxonase-1 (PON1) is an HDL-associated anti-atherogenic enzyme. The activity of PON1 is affected by the methionine for leucine substitution at position 55 (M55L) and increased during regular moderate alcohol consumption, consistent with increased HDL cholesterol concentration. We related the PON1 M55L genotypes to the extent of atherosclerosis in left anterior descending coronary artery (LAD) in alcohol abstainers (0-1 g of alcohol/day), moderate consumers (1-36 g of alcohol/day) and drinkers (> 36 g of alcohol/day). The study subjects included an autopsy series of total of 700 middle-aged Finnish men from the Helsinki Sudden Death Study. The LAD was stained for fat and the areas covered with fatty streaks and fibrotic and complicated plaques were measured. Data on coronary artery disease risk factors were obtained from relatives or close friends of the deceased. Compared to the LL homozygotes, carriers of the M55 allele tended to have larger areas of atherosclerotic lesions, the size of which decreased dose-dependently by reported alcohol consumption. Moderate consumers carrying the M55 allele had significantly larger complicated plaques compared to the LL homozygotes drinking as much (P = 0.009). Among the M55 allele carriers, drinkers showed significantly smaller areas of fatty streaks compared to abstainers (P = 0.042) and moderate consumers (P < 0.001) (for the PON1 genotype by alcohol interaction, P = 0.078). Similarly, drinkers with the M55 allele also had statistically significantly smaller areas of complicated lesions than moderate consumers with the M55 allele (P < 0.0001) (for the PON1 genotype by alcohol interaction, P = 0.009). The areas of atherosclerotic lesions in LAD appear to be dependent on the amount of alcohol consumption, especially in men carrying the PON1 M55 allele.