Functional COMT Val158Met polymorphism, risk of acute coronary events and serum homocysteine: the Kuopio ischaemic heart disease risk factor study

• Published in: PloS one Vol. 2; no. 1; p. e181
• Main Authors: Voutilainen, Sari, Tuomainen, Tomi-Pekka, Korhonen, Maarit, Mursu, Jaakko, Virtanen, Jyrki K, Happonen, Pertti, Alfthan, Georg, Erlund, Iris, North, Kari E, Mosher, M J, Kauhanen, Jussi, Tiihonen, Jari, Kaplan, George A, Salonen, Jukka T
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 31.01.2007; Public Library of Science (PLoS)
• Subjects: Adult; Alcohol; Antisocial personality disorder; Atherosclerosis; Blood cholesterol; Blood levels; Blood pressure; Cardiovascular disease; Cardiovascular diseases; Cardiovascular Disorders/Myocardial Infarction; Catechol; Catechol O-methyltransferase; Catechol O-Methyltransferase - genetics; Cholesterol; Cohort Studies; Confidence intervals; Coronary artery disease; Coronary Disease - blood; Coronary Disease - genetics; Coronary heart disease; Diabetes; Diet; Enzymes; Epidemiology; Folic acid; Folic Acid - blood; Gene polymorphism; Genetic aspects; Genetic factors; Genetic polymorphisms; Genetic Predisposition to Disease; Genetics and Genomics/Genetics of Disease; Genetics and Genomics/Medical Genetics; Genotype; Genotype & phenotype; Health risk assessment; Health risks; Heart; Heart attacks; Heart diseases; High density lipoprotein; Homocysteine; Homocysteine - blood; Humans; Hypertension; Hypotheses; Ischemia; Kaplan-Meier Estimate; Laboratories; Lipoproteins; Low density lipoprotein; Low density lipoproteins; Male; Medical research; Men; Metabolism; Methyltransferase; Middle Aged; Myocardial Ischemia - blood; Myocardial Ischemia - genetics; Nutrition; Nutrition research; Physiological aspects; Polymerase chain reaction; Polymorphism; Polymorphism, Genetic; Population; Population genetics; Population studies; Prospective Studies; Public health; Public Health and Epidemiology; Risk Factors; Smoking; Studies; Transferases; Triglycerides; Vitamin B; North Carolina; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0000181

The role of circulating levels of total homocysteine tHcy in the development of coronary heart disease (CHD) is still under debate. One reason for conflicting results between previous studies on homocysteine and heart diseases could be consequence of different interactions between homocysteine and genes in different study populations. Many genetic factors play a role in folate-homocysteine metabolism, like functional polymorphism (Val108Met) in the Catechol-O-methyltransferase (COMT) gene. Our aim was to examine the role of COMT Val158Met polymorphism and interaction of this polymorphism with serum tHcy and folate concentration on the risk of acute coronary and events in middle-aged men from eastern Finland. A population-based prospective cohort of 792 men aged 46-64 years was examined as part of the Kuopio Ischaemic Heart Disease Risk Factor Study. During an average follow-up of 9.3 years, there were 69 acute coronary events in men with no previous history of CHD. When comparing the COMT low activity genotype with the others, we found an age and examination year adjusted hazard rate ratio (HRR) of 1.73 (95% confidence interval (CI), 1.07-2.79), and an age, examination year, serum LDL and HDL cholesterol, and triglyceride concentration, systolic blood pressure and smoking adjusted HRR of 1.77 (95% CI, 1.05-2.77). Although serum tHcy concentration was not statistically significantly associated with acute coronary events (HRR for the highest third versus others 1.52, 95% CI, 0.93-2.49), subjects with both high serum tHcy and the COMT low activity genotype had an additionally increased adjusted risk of HRR 2.94 (95% CI 1.50-5.76) as compared with other men. This prospective cohort study suggests that the functional COMT Val158Met polymorphism is associated with increased risk of acute coronary events and it may interact with high serum tHcy levels.