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 WhittakerLon Cardon, Vincent Mooser

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Article numbere18208
JournalPloS one
Volume6
Issue number4
DOIs
Publication statusPublished - 2011 Apr 11

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1-Alkyl-2-acetylglycerophosphocholine Esterase
Gene encoding
phospholipase A2
null alleles
lipoproteins
Coronary Artery Disease
Alleles
Genes
genes
alleles
Plasmas
coronary artery disease
enzyme inhibition
Enzyme activity
Enzymes
Medical problems
case-control studies
Gene Frequency
epidemiological studies
gene frequency

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Jang, Yangsoo ; Waterworth, Dawn ; Lee, Jong Eun ; Song, Kijoung ; Kim, Sujin ; Kim, Hyo Soo ; Park, Kyung Woo ; Cho, Hyun Jai ; Oh, Il Young ; Park, Jeong Euy ; Lee, Bok Soo ; Ku, Hyo Jeong ; Shin, Dong Jik ; Lee, Jong Ho ; Jee, Sun Ha ; Han, Bok Ghee ; Jang, Hye Yoon ; Cho, Eun Young ; Vallance, Patrick ; Whittaker, John ; Cardon, Lon ; Mooser, Vincent. / Carriage of the V279F null allele within the gene encoding Lp-PLA2 is protective from coronary artery disease in South Korean males. In: PloS one. 2011 ; Vol. 6, No. 4.
@article{5e649d03b2c24d4bb409264e0aa3dbb7,
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. 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.",
author = "Yangsoo Jang and Dawn Waterworth and Lee, {Jong Eun} and Kijoung Song and Sujin Kim and Kim, {Hyo Soo} and Park, {Kyung Woo} and Cho, {Hyun Jai} and Oh, {Il Young} and Park, {Jeong Euy} and Lee, {Bok Soo} and Ku, {Hyo Jeong} and Shin, {Dong Jik} and Lee, {Jong Ho} and Jee, {Sun Ha} and Han, {Bok Ghee} and Jang, {Hye Yoon} and Cho, {Eun Young} and Patrick Vallance and John Whittaker and Lon Cardon and Vincent Mooser",
year = "2011",
month = "4",
day = "11",
doi = "10.1371/journal.pone.0018208",
language = "English",
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Jang, Y, Waterworth, D, Lee, JE, Song, K, Kim, S, Kim, HS, Park, KW, Cho, HJ, Oh, IY, Park, JE, Lee, BS, Ku, HJ, Shin, DJ, Lee, JH, Jee, SH, Han, BG, Jang, HY, Cho, EY, Vallance, P, Whittaker, J, Cardon, L & Mooser, V 2011, 'Carriage of the V279F null allele within the gene encoding Lp-PLA2 is protective from coronary artery disease in South Korean males', PloS one, vol. 6, no. 4, e18208. https://doi.org/10.1371/journal.pone.0018208

Carriage of the V279F null allele within the gene encoding Lp-PLA2 is protective from coronary artery disease in South Korean males. / Jang, Yangsoo; Waterworth, Dawn; Lee, Jong Eun; Song, Kijoung; Kim, Sujin; Kim, Hyo Soo; Park, Kyung Woo; Cho, Hyun Jai; Oh, Il Young; Park, Jeong Euy; Lee, Bok Soo; Ku, Hyo Jeong; Shin, Dong Jik; Lee, Jong Ho; Jee, Sun Ha; Han, Bok Ghee; Jang, Hye Yoon; Cho, Eun Young; Vallance, Patrick; Whittaker, John; Cardon, Lon; Mooser, Vincent.

In: PloS one, Vol. 6, No. 4, e18208, 11.04.2011.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Carriage of the V279F null allele within the gene encoding Lp-PLA2 is protective from coronary artery disease in South Korean males

AU - Jang, Yangsoo

AU - Waterworth, Dawn

AU - Lee, Jong Eun

AU - Song, Kijoung

AU - Kim, Sujin

AU - Kim, Hyo Soo

AU - Park, Kyung Woo

AU - Cho, Hyun Jai

AU - Oh, Il Young

AU - Park, Jeong Euy

AU - Lee, Bok Soo

AU - Ku, Hyo Jeong

AU - Shin, Dong Jik

AU - Lee, Jong Ho

AU - Jee, Sun Ha

AU - Han, Bok Ghee

AU - Jang, Hye Yoon

AU - Cho, Eun Young

AU - Vallance, Patrick

AU - Whittaker, John

AU - Cardon, Lon

AU - Mooser, Vincent

PY - 2011/4/11

Y1 - 2011/4/11

N2 - 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.

AB - 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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