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 Whittaker, Lon Cardon and Vincent Mooser

PLOS ONE, 2011, vol. 6, issue 4, 1-7

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.

Date: 2011
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0018208

DOI: 10.1371/journal.pone.0018208

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