title: Association between the Ala379Val variant of the lipoprotein associated phospholipase A2 and risk of myocardial infarction in the north and south of Europe.
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-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-PLA(2), strongly support the pro-inflammatory causative, and not consequential, role of Lp-PLA(2) in CHD.
authors.affiliation: Division of Cardiovascular Genetics, Department of Medicine, British Heart Foundation Laboratories, Rayne Building, Royal Free and University College Medical School, 5 University St, London WC1E 6JJ, UK.
authors.forename: A M
authors.initials: AM
authors.lastname: Abuzeid
authors.forename: E
authors.initials: E
authors.lastname: Hawe
authors.forename: S E
authors.initials: SE
authors.lastname: Humphries
authors.forename: Philippa J
authors.initials: PJ
authors.lastname: Talmud
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000409:Alanine; D000483:Alleles; D016022:Case-Control Studies; D005060:Europe; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics*; D016017:Odds Ratio; D010741:Phospholipases A / Q000235:genetics*; D054467:Phospholipases A2; D014633:Valine
chemical_list: D010741:Phospholipases A; D054467:Phospholipases A2; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D014633:Valine; D000409:Alanine