ORIGINAL ARTICLESAssociation of paraoxonase-1 M55L genotype and alcohol consumption with coronary atherosclerosis: the Helsinki Sudden Death StudyRontu, Riikkaa; Lehtimäki, Terhoa; Ilveskoski, Erkkia,b; Mikkelsson, Jussib; Kajander, Ollib; Goebeler, Sirkkab; Perola, Markusc; Penttilä, Anttid; Karhunen, Pekka JbAuthor Information aLaboratory of Atherosclerosis Genetics, Tampere University Hospital, Centre for Laboratory Medicine and Department of Clinical Chemistry, University of Tampere, Medical School, Tampere, bDepartment of Forensic Medicine, University of Tampere, Medical School and Research Unit of Tampere University Hospital, Tampere, cDepartment of Human Molecular Genetics, National Public Health Institute, Helsinki and dDepartment of Forensic Medicine, University of Helsinki, Helsinki, Finland. Sponsorship: The study was supported by grants from the Medical Research Fund of the Tampere University Hospital, the Finnish Foundation for Cardiovascular Research, the Emil Aaltonen Foundation, the Yrjö Jahnsson Foundation, the Finnish Foundation of Alcohol Research, the Elli and Elvi Oksanen Fund and the Pirkanmaa Regional Fund of the Finnish Cultural Foundation. Correspondence and requests for reprints to Riikka Rontu, Tampere University Hospital, Laboratory of Atherosclerosis Genetics, FinnMedi 2, Third Floor, PO Box 2000, FIN-33521 Tampere, Finland. Tel: +358 331174051; fax: +358 331174168; e-mail: [email protected] Received 3 February 2004 Accepted 16 April 2004 Pharmacogenetics: August 2004 - Volume 14 - Issue 8 - p 479-485 doi: 10.1097/01.fpc.0000114746.08559.00 Buy Metrics Abstract 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. © 2004 Lippincott Williams & Wilkins, Inc.