title: Carriage of the V279F null allele within the gene encoding Lp-PLA₂ is protective from coronary artery disease in South Korean males.
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.
  
  
  RESULTS
  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.
authors.affiliation: Division of Cardiology, Cardiovascular Genome Center, Yonsei University College of Medicine, Yonsei, South Korea.
authors.forename: Yangsoo
authors.initials: Y
authors.lastname: Jang
authors.forename: Dawn
authors.initials: D
authors.lastname: Waterworth
authors.forename: Jong-Eun
authors.initials: JE
authors.lastname: Lee
authors.forename: Kijoung
authors.initials: K
authors.lastname: Song
authors.forename: Sujin
authors.initials: S
authors.lastname: Kim
authors.forename: Hyo-Soo
authors.initials: HS
authors.lastname: Kim
authors.forename: Kyung Woo
authors.initials: KW
authors.lastname: Park
authors.forename: Hyun-Jai
authors.initials: HJ
authors.lastname: Cho
authors.forename: Il-Young
authors.initials: IY
authors.lastname: Oh
authors.forename: Jeong Euy
authors.initials: JE
authors.lastname: Park
authors.forename: Bok-Soo
authors.initials: BS
authors.lastname: Lee
authors.forename: Hyo Jeong
authors.initials: HJ
authors.lastname: Ku
authors.forename: Dong-Jik
authors.initials: DJ
authors.lastname: Shin
authors.forename: Jong Ho
authors.initials: JH
authors.lastname: Lee
authors.forename: Sun Ha
authors.initials: SH
authors.lastname: Jee
authors.forename: Bok-Ghee
authors.initials: BG
authors.lastname: Han
authors.forename: Hye-Yoon
authors.initials: HY
authors.lastname: Jang
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Cho
authors.forename: Patrick
authors.initials: P
authors.lastname: Vallance
authors.forename: John
authors.initials: J
authors.lastname: Whittaker
authors.forename: Lon
authors.initials: L
authors.lastname: Cardon
authors.forename: Vincent
authors.initials: V
authors.lastname: Mooser
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000235:genetics*; D000483:Alleles; D044466:Asian People; D003324:Coronary Artery Disease / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D056910:Republic of Korea
chemical_list: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase