Carriage of the V279F null allele within the gene encoding Lp-PLA2 is protective from coronary artery disease in South Korean males

Yangsoo Jang, Dawn Waterworth, Jong Eun Lee, Kijoung Song, Sujin Kim, Hyo Soo Kim, Kyung Woo Park, Hyun Jai Cho, Il Young Oh, Jeong Euy Park, Bok Soo Lee, Hyo Jeong Ku, Dong Jik Shin, Jong Ho Lee, Sun Ha Jee, Bok Ghee Han, Hye Yoon Jang, Eun Young Cho, Patrick Vallance, John WhittakerLon Cardon, Vincent Mooser

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Abstract

Background: The Asia-specific PLA2G7 994G-T transversion leads to V279F substitution within the lipoprotein-associated phospholipase-A2 (Lp-PLA2) and to absence of enzyme activity in plasma. This variant offers a unique natural experiment to assess the role of Lp-PLA2 in the pathogenesis of coronary artery disease (CAD) in humans. Given conflicting results from mostly small studies, a large two-stage case-control study was warranted. Methodology/Principal Findings: PLA2G7 V279F genotypes were initially compared in 2890 male cases diagnosed with CAD before age 60 with 3128 male controls without CAD at age 50 and above and subsequently in a second independent male dataset of 877 CAD cases and 1230 controls. In the first dataset, the prevalence of the 279F null allele was 11.5% in cases and 12.8% in controls. After adjustment for age, body mass index, diabetes, smoking, glucose and lipid levels, the OR (95% CI) for CAD for this allele was 0.80 (0.66-0.97, p = 0.02). The results were very similar in the second dataset, despite lower power, with an allele frequency of 11.2% in cases and 12.5% in controls, leading to a combined OR of 0.80 (0.69-0.92), p = 0.002. The magnitude and direction of this genetic effect were fully consistent with large epidemiological studies on plasma Lp-PLA2 activity and CAD risk. Conclusions: Natural deficiency in Lp-PLA2 activity due to carriage of PLA2G7 279F allele protects from CAD in Korean men. These results provide evidence for a causal relationship between Lp-PLA2 and CAD, and support pharmacological inhibition of this enzyme as an innovative way to prevent CAD.

Original languageEnglish
Article numbere18208
JournalPloS one
Volume6
Issue number4
DOIs
Publication statusPublished - 2011

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Jang, Y., Waterworth, D., Lee, J. E., Song, K., Kim, S., Kim, H. S., Park, K. W., Cho, H. J., Oh, I. Y., Park, J. E., Lee, B. S., Ku, H. J., Shin, D. J., Lee, J. H., Jee, S. H., Han, B. G., Jang, H. Y., Cho, E. Y., Vallance, P., ... Mooser, V. (2011). Carriage of the V279F null allele within the gene encoding Lp-PLA2 is protective from coronary artery disease in South Korean males. PloS one, 6(4), [e18208]. https://doi.org/10.1371/journal.pone.0018208