Functional COMT Val158Met Polymorphism, Risk of Acute Coronary Events and Serum Homocysteine: The Kuopio Ischaemic Heart Disease Risk Factor Study

Abstract

BackgroundThe 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.Methodology and FindingsOur 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.ConclusionsThis 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.

The Response of Human Colonocytes to Folate Deficiency in Vitro: Functional and Proteomic Analyses

“…A common polymorphism (val 108 met) in the COMT gene 39 is associated with an increased risk of acute coronary events. 40 Low folate intake is associated with an increased breast cancer risk, as is decreased COMT activity. [41][42][43] Low folate intake in combination with low COMT activity (met 158 polymorphism) predicts a higher risk for breast cancer.…”

Angiogenic defects in preeclampsia: What is known, and how are such defects relevant to preeclampsia pathogenesis?

“…60) Men with high serum homocysteine levels who are also homozygous for the low-activity Comt gene (Val158Met isoform; COMT LL ) are at increased risk of coronary heart disease. 61) This finding may be relevant to the pathogenesis of preeclampsia in women who are homozygous for COMT LL . The possibility that homocysteine-induced preeclampsia is dependent on Comt genotype could be why hyperhomocysteinemia did not lead to preeclampsia in previous animal studies with wild-type rodents.…”

Catechol-O-methyltransferase promoter hypomethylation is associated with the risk of coronary heart disease

“…Therefore, COMT, as a homocysteine metabolism-mediated gene, has been hypothesized to serve a vital role in the increased risk of CHD (17). A low activity COMT genotype has a protective effect against cardiovascular diseases (23).…”

“…Furthermore, a number of studies have revealed an association between COMT and metabolic syndromes, such as hypertension and diabetes, that are closely associated with CHD (15,16). COMT gene variation serves an important role in the increased risk of acute coronary events (17).…”