Association between the Ala379Val variant of the lipoprotein associated phospholipase A2 and risk of myocardial infarction in the north and south of Europe

A. M. Abuzeid, E. Hawe, S. E. Humphries, Philippa J. Talmud, P. Lundman, A. Samnegard, A. Silveira, P. Tornvall, J. Yudkin, V. Mohamed-Ali, A. Holmes, S. E. Humphries, E. Hawe, L. Ahn Luong, I. Juhan-Vague, M. F. Aillaud, P. E. Morange, M. C. Alessi, P. Ambrosi, I. Canavy & 18 others F. Paganelli, R. Didelot, J. Ansaldi, M. Billerey, Minno Di, M. Margaglione, D. Cimino, N. Dello Iacono, A. Cimino, G. Gaeta, C. Blasich, G. Pucciarelli, V. van Hinsbergh, T. Kooistra, E. Tremoli, C. Banfi, L. Mussoni, The HIFMECH Study Group

Research output: Contribution to journalArticle

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Abstract

Lipoprotein-associated phospholipase A2(Lp-PLA2) has been identified as a coronary heart disease (CHD) risk predictor. Both its anti-inflammatory role by hydrolysing platelet activating factor, and pro-inflammatory generation of atherogenic mediators may influence CHD risk. We investigated the association of the activity-reducing A379V variant with risk of myocardial infarction (MI) in a large European case-control study, which compared 527 post-MI men with 566 age-matched controls from north and south Europe. Overall, the frequency of the V379 allele was 0.24 (95%CI 0.21-0.26), with no evidence for differences between centres. Homozygosity for the V379 allele was associated with lower risk of MI, (Odds Ratio (OR) 0.56, 95%CI 0.32-0.98), maintained after adjustment for lifestyle factors and levels of inflammatory risk factors (C-reactive protein, fibrinogen, IL-6) (OR 0.46, 0.22-0.93). There was no evidence of heterogeneity of effect between the centres in the north and south of Europe (P-value for interaction=0.80). Since homozygosity for V379 occurs in only 5-6% of subjects, this genotype is not a major determinant of population genetic risk of CHD, but the association of this genotype with low levels of Lp-PLA2, strongly support the pro-inflammatory causative, and not consequential, role of Lp-PLA2in CHD.

Original languageEnglish
Pages (from-to)283-288
Number of pages6
JournalAtherosclerosis
Volume168
Issue number2
DOIs
Publication statusPublished - Jun 1 2003

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1-Alkyl-2-acetylglycerophosphocholine Esterase
Myocardial Infarction
Coronary Disease
Odds Ratio
Genotype
Platelet Activating Factor
Population Genetics
Gene Frequency
C-Reactive Protein
Fibrinogen
Case-Control Studies
Life Style
Interleukin-6
Anti-Inflammatory Agents
Alleles

Keywords

  • Lipoprotein associated PLA2
  • PAFAH
  • PLA2G7
  • Polymorphism

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Abuzeid, A. M., Hawe, E., Humphries, S. E., Talmud, P. J., Lundman, P., Samnegard, A., ... The HIFMECH Study Group (2003). Association between the Ala379Val variant of the lipoprotein associated phospholipase A2 and risk of myocardial infarction in the north and south of Europe. Atherosclerosis, 168(2), 283-288. https://doi.org/10.1016/S0021-9150(03)00086-8

Association between the Ala379Val variant of the lipoprotein associated phospholipase A2 and risk of myocardial infarction in the north and south of Europe. / Abuzeid, A. M.; Hawe, E.; Humphries, S. E.; Talmud, Philippa J.; Lundman, P.; Samnegard, A.; Silveira, A.; Tornvall, P.; Yudkin, J.; Mohamed-Ali, V.; Holmes, A.; Humphries, S. E.; Hawe, E.; Ahn Luong, L.; Juhan-Vague, I.; Aillaud, M. F.; Morange, P. E.; Alessi, M. C.; Ambrosi, P.; Canavy, I.; Paganelli, F.; Didelot, R.; Ansaldi, J.; Billerey, M.; Di, Minno; Margaglione, M.; Cimino, D.; Dello Iacono, N.; Cimino, A.; Gaeta, G.; Blasich, C.; Pucciarelli, G.; van Hinsbergh, V.; Kooistra, T.; Tremoli, E.; Banfi, C.; Mussoni, L.; The HIFMECH Study Group.

In: Atherosclerosis, Vol. 168, No. 2, 01.06.2003, p. 283-288.

Research output: Contribution to journalArticle

Abuzeid, AM, Hawe, E, Humphries, SE, Talmud, PJ, Lundman, P, Samnegard, A, Silveira, A, Tornvall, P, Yudkin, J, Mohamed-Ali, V, Holmes, A, Humphries, SE, Hawe, E, Ahn Luong, L, Juhan-Vague, I, Aillaud, MF, Morange, PE, Alessi, MC, Ambrosi, P, Canavy, I, Paganelli, F, Didelot, R, Ansaldi, J, Billerey, M, Di, M, Margaglione, M, Cimino, D, Dello Iacono, N, Cimino, A, Gaeta, G, Blasich, C, Pucciarelli, G, van Hinsbergh, V, Kooistra, T, Tremoli, E, Banfi, C, Mussoni, L & The HIFMECH Study Group 2003, 'Association between the Ala379Val variant of the lipoprotein associated phospholipase A2 and risk of myocardial infarction in the north and south of Europe', Atherosclerosis, vol. 168, no. 2, pp. 283-288. https://doi.org/10.1016/S0021-9150(03)00086-8
Abuzeid, A. M. ; Hawe, E. ; Humphries, S. E. ; Talmud, Philippa J. ; Lundman, P. ; Samnegard, A. ; Silveira, A. ; Tornvall, P. ; Yudkin, J. ; Mohamed-Ali, V. ; Holmes, A. ; Humphries, S. E. ; Hawe, E. ; Ahn Luong, L. ; Juhan-Vague, I. ; Aillaud, M. F. ; Morange, P. E. ; Alessi, M. C. ; Ambrosi, P. ; Canavy, I. ; Paganelli, F. ; Didelot, R. ; Ansaldi, J. ; Billerey, M. ; Di, Minno ; Margaglione, M. ; Cimino, D. ; Dello Iacono, N. ; Cimino, A. ; Gaeta, G. ; Blasich, C. ; Pucciarelli, G. ; van Hinsbergh, V. ; Kooistra, T. ; Tremoli, E. ; Banfi, C. ; Mussoni, L. ; The HIFMECH Study Group. / Association between the Ala379Val variant of the lipoprotein associated phospholipase A2 and risk of myocardial infarction in the north and south of Europe. In: Atherosclerosis. 2003 ; Vol. 168, No. 2. pp. 283-288.
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abstract = "Lipoprotein-associated phospholipase A2(Lp-PLA2) has been identified as a coronary heart disease (CHD) risk predictor. Both its anti-inflammatory role by hydrolysing platelet activating factor, and pro-inflammatory generation of atherogenic mediators may influence CHD risk. We investigated the association of the activity-reducing A379V variant with risk of myocardial infarction (MI) in a large European case-control study, which compared 527 post-MI men with 566 age-matched controls from north and south Europe. Overall, the frequency of the V379 allele was 0.24 (95{\%}CI 0.21-0.26), with no evidence for differences between centres. Homozygosity for the V379 allele was associated with lower risk of MI, (Odds Ratio (OR) 0.56, 95{\%}CI 0.32-0.98), maintained after adjustment for lifestyle factors and levels of inflammatory risk factors (C-reactive protein, fibrinogen, IL-6) (OR 0.46, 0.22-0.93). There was no evidence of heterogeneity of effect between the centres in the north and south of Europe (P-value for interaction=0.80). Since homozygosity for V379 occurs in only 5-6{\%} of subjects, this genotype is not a major determinant of population genetic risk of CHD, but the association of this genotype with low levels of Lp-PLA2, strongly support the pro-inflammatory causative, and not consequential, role of Lp-PLA2in CHD.",
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AU - Abuzeid, A. M.

AU - Hawe, E.

AU - Humphries, S. E.

AU - Talmud, Philippa J.

AU - Lundman, P.

AU - Samnegard, A.

AU - Silveira, A.

AU - Tornvall, P.

AU - Yudkin, J.

AU - Mohamed-Ali, V.

AU - Holmes, A.

AU - Humphries, S. E.

AU - Hawe, E.

AU - Ahn Luong, L.

AU - Juhan-Vague, I.

AU - Aillaud, M. F.

AU - Morange, P. E.

AU - Alessi, M. C.

AU - Ambrosi, P.

AU - Canavy, I.

AU - Paganelli, F.

AU - Didelot, R.

AU - Ansaldi, J.

AU - Billerey, M.

AU - Di, Minno

AU - Margaglione, M.

AU - Cimino, D.

AU - Dello Iacono, N.

AU - Cimino, A.

AU - Gaeta, G.

AU - Blasich, C.

AU - Pucciarelli, G.

AU - van Hinsbergh, V.

AU - Kooistra, T.

AU - Tremoli, E.

AU - Banfi, C.

AU - Mussoni, L.

AU - The HIFMECH Study Group

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N2 - Lipoprotein-associated phospholipase A2(Lp-PLA2) has been identified as a coronary heart disease (CHD) risk predictor. Both its anti-inflammatory role by hydrolysing platelet activating factor, and pro-inflammatory generation of atherogenic mediators may influence CHD risk. We investigated the association of the activity-reducing A379V variant with risk of myocardial infarction (MI) in a large European case-control study, which compared 527 post-MI men with 566 age-matched controls from north and south Europe. Overall, the frequency of the V379 allele was 0.24 (95%CI 0.21-0.26), with no evidence for differences between centres. Homozygosity for the V379 allele was associated with lower risk of MI, (Odds Ratio (OR) 0.56, 95%CI 0.32-0.98), maintained after adjustment for lifestyle factors and levels of inflammatory risk factors (C-reactive protein, fibrinogen, IL-6) (OR 0.46, 0.22-0.93). There was no evidence of heterogeneity of effect between the centres in the north and south of Europe (P-value for interaction=0.80). Since homozygosity for V379 occurs in only 5-6% of subjects, this genotype is not a major determinant of population genetic risk of CHD, but the association of this genotype with low levels of Lp-PLA2, strongly support the pro-inflammatory causative, and not consequential, role of Lp-PLA2in CHD.

AB - Lipoprotein-associated phospholipase A2(Lp-PLA2) has been identified as a coronary heart disease (CHD) risk predictor. Both its anti-inflammatory role by hydrolysing platelet activating factor, and pro-inflammatory generation of atherogenic mediators may influence CHD risk. We investigated the association of the activity-reducing A379V variant with risk of myocardial infarction (MI) in a large European case-control study, which compared 527 post-MI men with 566 age-matched controls from north and south Europe. Overall, the frequency of the V379 allele was 0.24 (95%CI 0.21-0.26), with no evidence for differences between centres. Homozygosity for the V379 allele was associated with lower risk of MI, (Odds Ratio (OR) 0.56, 95%CI 0.32-0.98), maintained after adjustment for lifestyle factors and levels of inflammatory risk factors (C-reactive protein, fibrinogen, IL-6) (OR 0.46, 0.22-0.93). There was no evidence of heterogeneity of effect between the centres in the north and south of Europe (P-value for interaction=0.80). Since homozygosity for V379 occurs in only 5-6% of subjects, this genotype is not a major determinant of population genetic risk of CHD, but the association of this genotype with low levels of Lp-PLA2, strongly support the pro-inflammatory causative, and not consequential, role of Lp-PLA2in CHD.

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KW - Polymorphism

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