4G/5G polymorphism and haplotypes of SERPINE1 in atherosclerotic diseases of coronary arteries.
We assessed the association between common variation at the SERPINE1 (PAI1) locus and myocardial infarction (MI). Haplotype-tagging polymorphisms, including the 4G/5G deletion/insertion polymorphism and seven single nucleotide polymorphisms, were analysed in a German sample containing 3,657 cases with MI and 1,211 controls. The association between the 4G/5G polymorphism and MI was examined in a meta-analysis of data extracted from 32 studies (13,267 cases/14,716 controls). In addition, the relation between the 4G/5G polymorphism and coronary diseases, comprising MI, coronary artery disease, coronary heart disease, or the acute coronary syndrome, was assessed in a combined analysis enclosing 43 studies (17,278 cases/18,039 controls). None of the tagging polymorphisms was associated with MI in the present sample (p <or= 0.34). The adjusted odds ratio (OR) for 4G allele carriers was 1.02 (95% confidence interval [CI] 0.87-1.19) compared to the 5G5G genotype. None of 13 common (frequency >1.0%) 8-marker haplotypes was related to the risk of MI. In a meta-analysis specifically addressing the association with MI, no elevated risk was found in the carriers of the 4G allele (OR 1.07, 95% CI 0.99-1.16; p = 0.11). A more general combined analysis of coronary diseases showed a marginally increased risk in 4G allele carriers (OR 1.08, 95% CI 1.00-1.16; p = 0.044). In essence, tagging polymorphisms, including the 4G/5G polymorphism, and common haplotypes of the SERPINE1 gene region were not associated with MI in a German sample, and no compelling evidence was obtained for a relationship of the 4G/5G polymorphism to MI and coronary atherosclerosis in a meta-analysis.
Koch
Werner
W
Deutsches Herzzentrum München, 1. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. wkoch@dhm.mhn.de
Schrempf
Matthias
M
Erl
Anna
A
Mueller
Jakob C
JC
Hoppmann
Petra
P
Schömig
Albert
A
Kastrati
Adnan
A
D000368:Aged; D000818:Animals; D003324:Coronary Artery Disease / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D005260:Female; D056726:Genetic Association Studies; D005858:Germany; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009203:Myocardial Infarction; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D011110:Polymorphism, Genetic
D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human