Human Molecular Genetics, Vol 7, 1453-1462, Copyright © 1998 by Oxford University Press
T Pastinen, M Perola, P Niini, J Terwilliger, V Salomaa, E Vartiainen, L Peltonen and A Syvanen
We analysed common variants of eight genes implicated previously as risk
factors for coronary heart disease or myocardial infarction (MI) in a
cross-sectional study on patients with a history of MI and in carefully
matched controls from the Finnish population. The most common low density
lipoprotein receptor mutations in Finland were also included in our
analysis. Multiplex genotyping of the target genes was performed using a
specific and efficient array-based minisequencing system. The 4G allele of
the plasminogen activator inhibitor gene (P < 0.05) and the PlA2 allele
of the glycoprotein IIIa gene (P < 0.01) were associated with an
increased risk of MI in our study population. We analysed the combined
effect of these risk alleles and found that the concurrent carrier status
of the two genetic variants conferred a high risk for the development of MI
in our sample (OR = 4.5, P = 0.001), which was particularly prominent in
male subjects (OR = 6.4, P = 0.0005). This study demonstrates the
application of a new powerful tool for genome analysis to yield information
on the inherited determinants of susceptibility to MI. The observation of
two separate genes contributing an additive risk of developing MI
exemplifies the advantages of multiplex analysis of genetic variation.
ARTICLES
Array-based multiplex analysis of candidate genes reveals two independent and additive genetic risk factors for myocardial infarction in the Finnish population
Department of Human Molecular Genetics, National Public Health Institute, Mannerheimintie 166, FIN 00300, Helsinki, Finland. tomi.pastinen@ktl.fi
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