The Val279Phe variant of the lipoprotein-associated phospholipase A2 gene is associated with catalytic activities and cardiovascular disease in Korean men

Yangsoo Jang, Yoen Kim Oh, Jeong Koh Soo, Sook Chae Jey, Guk Ko Young, Young Kim Ji, Hongkeun Cho, Tae Sook Jeong, Song Lee Woo, Jose M. Ordovas, Jong Ho Lee

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Abstract

Context and Objective: It is unclear whether lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ) exerts a pro- or antiatherogenic effect on cardiovascular disease (CVD). We investigated the association between Lp-PLA 2 variant (V279F and A379V) and CVD in Korean men. Design: CVD patients (n = 532) and healthy controls (n = 670) were genotyped for the Lp-PLA 2 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-PLA 2 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-PLA 2 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-PLA 2 plays a proatherogenic and causative role in CVD.

Original languageEnglish
Pages (from-to)3521-3527
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume91
Issue number9
DOIs
Publication statusPublished - 2006 Jan 1

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All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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