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

Authors
 Yangsoo Jang ; Dawn Waterworth ; Vincent Mooser ; Lon Cardon ; John Whittaker ; Patrick Vallance ; Eun-Young Cho ; Hye-Yoon Jang ; Bok-Ghee Han ; Sun Ha Jee ; Jong Ho Lee ; Dong-Jik Shin ; Hyo Jeong Ku ; Bok-Soo Lee ; Jeong Euy Park ; Il-Young Oh ; Hyun-Jai Cho ; Kyung Woo Park ; Hyo-Soo Kim ; Sujin Kim ; Kijoung Song ; Jong-Eun Lee 
Citation
 PLoS One, Vol.6(4) : e18208, 2011 
Journal Title
 PLoS One 
ISSN
 1932-6203 
Issue Date
2011
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.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/94844
DOI
10.1371/journal.pone.0018208
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Internal Medicine
1. 연구논문 > 4. Graduate School of Public Health > Graduate School of Public Health
Yonsei Authors
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