Carriage of the V279F Null Allele within the Gene Encoding Lp-PLA(2) Is Protective from Coronary Artery Disease in South Korean Malesopen access
- Authors
- Jang, Y[Jang, Yangsoo]; Waterworth, D[Waterworth, Dawn]; Lee, JE[Lee, Jong-Eun]; Song, K[Song, Kijoung]; Kim, S[Kim, Sujin]; Kim, HS[Kim, Hyo-Soo]; Park, KW[Park, Kyung Woo]; Cho, HJ[Cho, Hyun-Jai]; Oh, IY[Oh, Il-Young]; Park, JE[Park, Jeong Euy]; Lee, BS[Lee, Bok-Soo]; Ku, HJ[Ku, Hyo Jeong]; Shin, DJ[Shin, Dong-Jik]; Lee, JH[Lee, Jong Ho]; Jee, SH[Jee, Sun Ha]; Han, BG[Han, Bok-Ghee]; Jang, HY[Jang, Hye-Yoon]; Cho, EY[Cho, Eun-Young]; Vallance, P[Vallance, Patrick]; Whittaker, J[Whittaker, John]; Cardon, L[Cardon, Lon]; Mooser, V[Mooser, Vincent]
- Issue Date
- 5-Apr-2011
- Citation
- PLOS ONE, v.6, no.4
- Indexed
- SCIE
SCOPUS
- Journal Title
- PLOS ONE
- Volume
- 6
- Number
- 4
- URI
- https://scholarworks.bwise.kr/skku/handle/2021.sw.skku/70279
- DOI
- 10.1371/journal.pone.0018208
- ISSN
- 1932-6203
- Abstract
- Background: The Asia-specific PLA2G7 994G-T transversion leads to V279F substitution within the lipoprotein-associated phospholipase-A2 (Lp-PLA(2)) and to absence of enzyme activity in plasma. This variant offers a unique natural experiment to assess the role of Lp-PLA(2) 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-PLA(2) activity and CAD risk. Conclusions: Natural deficiency in Lp-PLA(2) activity due to carriage of PLA2G7 279F allele protects from CAD in Korean men. These results provide evidence for a causal relationship between Lp-PLA(2) and CAD, and support pharmacological inhibition of this enzyme as an innovative way to prevent CAD.
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Collections - Medicine > Department of Medicine > 1. Journal Articles
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