Association of homocysteine thiolactonase activity and PON1 polymorphisms with the severity of acute coronary syndrome

Introduction: Excess of total homocysteine (tHcy) and decrease of thiolactonase activities (HTase) have been proposed as risk factors for coronary artery diseases (CAD). Objectives: We evaluated the relationship of tHey and HTase with paraoxonase 1 (PON1) gene polymorphism according to CAD severity. Design and methods: 118 healthy volunteers and 91 CAD patients were compared. Results: Serum levels of tHcy and oxidized LDL (ox-LDL) increased significantly by 26% and 49% in CAD patients and were associated with significantly lower levels of HDL cholesterol (p=0.02) and 42% of decrease in HTase activities (p<0.05). In these patients the HTase activity was negatively associated with tHcy and Hs CRP levels (r=-0.622, p=0.00 and r=-0.355, p=0.007 respectively) but positively associated,with apoB and triglyceride levels (r=0.35, p=0.042 and r=0.308, p=0.003 respectively). HTase activity decreased inversely to the number of affected vessels and according to PON1 polymorphism. PON1 Q192R RR and PON1 L55M MM genotypes were associated with higher HTase activities. Only PON1 L55M (MM) genotype frequency was significantly higher in CAD patients than in controls (P<0.05), while its Frequency was similar between the two Subgroups according to CAD severity. In a multivariate analysis, tHcy levels were the only independent factor affecting the severity of cardiovascular disease (p=0.029). Conclusions: High tHcy levels are associated with the severity of cardiovascular disease and may be partly explained by the diminished HTase activities in these patients. Crown Copyright (c) 2009 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.