Association of plasminogen activator inhibitor-1 4G/5G gene polymorphism with variations in the LDL particle size in healthy Japanese men

Background: Several studies have supported the association between a predominance of small, dense low-density lipoprotein (LDL) and the risk of coronary artery disease. As another potentially atherogenic factor, impaired fibrinolytic activity due to increased plasminogen activator inhibitor-1 (PAI-1) concentrations has been shown. In addition, the 4G allele of the 4G/5G polymorphism in the promoter region of the PAM gene is reported to be associated with the atherogenic lipid profile. We investigated the relation between the PAI-1 gene polymorphism and LDL particle size. Methods: A total of 156 healthy Japanese male subjects were recruited. The diameter of LDL particles was determined at their peak size using polyacrylamide gels using fresh plasma samples. Results: Fasting insulin and triglyceride concentrations were found to be significantly higher, and the LDL particle size was smaller in the homozygotes for the 5G allele than in the carriers of the 4G allele. An analysis of covariance (ANCOVA) adjusting for insulin and triglyceride concentrations showed a consistently significant difference in LDL particle size between the two groups. In the forward stepwise multiple regression analysis, triglycerides, insulin, and the PAI-1 5G/5G genotype remained in the model as independent and significant predictors capable of influencing the LDL particle size. Conclusions: Our findings suggest that the 4G/5G polymorphism of the PAI-1 gene might be associated with LDL particle size in healthy Japanese males. (C) 2004 Elsevier B.V. All rights reserved.