Context and Objective: It is unclear whether lipoprotein-associated phospholipase A2 (Lp-PLA2) exerts a pro- or antiatherogenic effect on cardiovascular disease (CVD). We investigated the association between Lp-PLA2 variant (V279F and A379V) and CVD in Korean men. Design: CVD patients (n = 532) and healthy controls (n = 670) were genotyped for the Lp-PLA2 polymorphism (V279F and A379V). Main Outcome Measures: We calculated odds ratio (OR) on CVD risk and measured anthropometries, lipid profiles, low-density lipoprotein (LDL) particle size, oxidized LDL, lipid peroxides, and Lp-PLA2 activity. Results: The presence of the 279F allele was associated with a lower risk of CVD [OR 0.646 (95% confidence interval 0.490-0.850), P = 0.002], and the association still remained after adjustments for age, body mass index, waist circumference, waist to hip ratio, cigarette smoking, and alcohol consumption [OR 0.683 (95% confidence interval 0.512-0.911), P = 0.009]. Lp-PLA2 activity was lower in CVD patients taking a lipid-lowering drug (31%), those not taking a lipid-lowering drug (26%), and control subjects (23%) with the V/F genotype, compared with those with the V/V genotype. Subjects with the F/F genotype in controls and two CVD patients groups showed no appreciable enzymatic activity. Control subjects with the V/F genotype had larger LDL particle size than those with the V/V genotype. In addition, control subjects carrying the F allele showed lower malondialdehyde concentrations. On the other hand, we found no significant relationship between A379V genotype and CVD risk. Conclusions: The association of the F279 loss of function variant with the reduced risk of CVD supports the concept that Lp-PLA2 plays a proatherogenic and causative role in CVD.
Bibliographical noteFunding Information:
This work was supported by the National Research Laboratory Project (2005–01572), Ministry of Science and Technology, Seoul, Korea; Korea Science and Engineering Foundation, Seoul, Korea (R01–2003–0000–11709–0); Korea Health 21 R&D Projects (00–PJ3-PG6-GN-01-0001), Ministry of Health and Welfare, Seoul, Korea; National Institutes of Health/National Heart, Lung, and Blood Institute (HL54776) and contracts 53-K06-5-10 and 58-1950-9-001 from the U.S. Department of Agriculture Research Service, Beltsville, MD.
All Science Journal Classification (ASJC) codes
- Endocrinology, Diabetes and Metabolism
- Clinical Biochemistry
- Biochemistry, medical