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

Abuzeid, AM; Hawe, E; Humphries, SE; Talmud, PJ; HIFMECH Study Grp,; (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. 10.1016/S0021-9150(03)00086-8.

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Abstract

Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) has been identified as a coronary heart disease (CHD) risk predictor. Both its anti-inflammatory role by hydrolysing platelet activating factor, and pro-inflaminatory 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-Ml 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-PLA(2), strongly support the pro-inflammatory causative, and not consequential, role of Lp-PLA(2) in CHD. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.

Type:Article
Title:Association between the Ala379Val variant of the lipoprotein associated phospholipase A2 and risk of myocardial infarction in the north and south of Europe
DOI:10.1016/S0021-9150(03)00086-8
Keywords:PLA2G7, lipoprotein associated PLA2, PAFAH, polymorphism, ACTIVATING-FACTOR ACETYLHYDROLASE, PAF-ACETYLHYDROLASE, DISEASE, A(2), LDL, ATHEROSCLEROSIS, DEFICIENCY, OXIDATION, INHIBITOR, GENOTYPE
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science

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