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The Val279Phe Variant of the Lipoprotein-Associated Phospholipase A2 Gene Is Associated with Catalytic Activities and Cardiovascular Disease in Korean Men

Division of Cardiology (Y.J., Y.K.G.), Cardiovascular Genome Center, Yonsei Medical Institute, Yonsei University Research Institute of Science for Aging (Y.J., O.Y.K., S.J.K., J.S.C., Y.K.G., J.Y.K., H.C., J.H.L.), Brain Korea 21 Project for Medical Science (S.J.K.), National Research Laboratory of Clinical Nutrigenetics/Nutrigenomics (J.H.L.), Yonsei University, Seoul 120-749, Korea; DNA Link Ltd. (J.Y.K.), Seoul 120-110, Korea; National Research Laboratory of Lipid Metabolism and Atherosclerosis (T.-S.J., W.S.L.), Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-333, Korea; and Nutrition and Genomics Laboratory (J.M.O.), Jean Mayer-U.S. Department of Agriculture-Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts 02111

Address all correspondence and requests for reprints to: Jong Ho Lee, Department of Food and Nutrition, Yonsei University, 134 Shinchon-Ding, Sudaemun-Gu, Seoul 120-749, Korea. E-mail: jhleeb{at}yonsei.ac.kr.

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.

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