Lipoprotein-associated phospholipase A2 is related to risk of subclinical atherosclerosis but is not supported by Mendelian randomization analysis in a general Japanese population

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Objective: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an enzyme predominantly bound to low-density lipoprotein (LDL). Lp-PLA2 is recognized as playing a key role in inflammatory processes and the development of atherosclerosis. This study aimed to investigate whether Lp-PLA2 is related to subclinical atherosclerosis, independently from traditional risk factors, in a general Japanese population by analyses of both the observational study and Mendelian randomization using V279F polymorphism. Methods and results: We cross-sectionally examined community-based sample of 929 Japanese men aged 40-79 years, without statin treatment, who were randomly selected from the resident registration. Multiple regression analyses of Lp-PLA2 activity and concentration were undertaken separately for men aged 40-49 years and 50-79 years, to clarify interactions of age and Lp-PLA2. Lp-PLA2 activity for men aged 50-79 years was significantly and positively related to intima-media thickness (IMT) (P = 0.013) and plaque index (P = 0.008) independent of traditional risk factors including small LDL particles, but not to coronary artery calcification (CAC) score. Associations with Lp-PLA2 concentration were qualitatively similar to those of activity. Corresponding relationships were not observed in men aged 40-49 years. Mendelian randomization analyses based on V279F genotype did not show any significant associations with subclinical atherosclerosis, although the homozygote and heterozygote of V279F showed low Lp-PLA2 activity and concentration. Conclusions: Lp-PLA2 activity in Japanese men aged 50-79 years was associated significantly and positively with IMT and plaque in the carotid artery but Mendelian randomization did not support that Lp-PLA2 is a causative factor for subclinical atherosclerosis.

Original languageEnglish
Pages (from-to)141-147
Number of pages7
Publication statusPublished - 2016 Mar 1


  • Carotid intima-media thickness
  • Carotid plaque
  • Coronary artery calcification
  • Lp-PLA
  • Mendelian randomization

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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