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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

 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  ;  Vincent Mooser 
 PLOS ONE, Vol.6(4) : e18208, 2011 
Journal Title
Issue Date
1-Alkyl-2-acetylglycerophosphocholine Esterase/genetics* ; Alleles ; Asian Continental Ancestry Group ; Coronary Artery Disease/genetics* ; Female ; Genetic Predisposition to Disease/genetics ; Genotype ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide/genetics ; Republic of Korea
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.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
4. Graduate School of Public Health (보건대학원) > Graduate School of Public Health (보건대학원) > 1. Journal Papers
Yonsei Authors
Jang, Yang Soo(장양수) ORCID logo https://orcid.org/0000-0002-2169-3112
Jee, Sun Ha(지선하) ORCID logo https://orcid.org/0000-0001-9519-3068
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