Abstract:
Coronary artery disease (CAD) is a multifactorial disease mediated by genetic and
environmental factors. The inflammatory pathway is one of the many pathways
which are implicated in CAD pathobiology. Recent studies defined several
inflammatory genes as susceptibility genes to CAD. Genetic variations in the
ALOX5AP gene coding for arachidonate 5-lipoxygenase-activating protein (FLAP)
have been shown to predispose to CAD in European populations. The aim of the
present study was to validate the role of the genetic variations of ALOX5AP gene in
CAD in a Lebanese population with angiographically established CAD. Four single
nucleotide polymorphisms (SNPs) (the at-risk haplotype B) in the ALOX5AP gene
were genotyped in 289 young CAD patients (> 50% stenosis, :::: 52 years) with
positive family history of CAD and 227 old subjects proved to be free of CAD ( 0%
stenosis, ~ 60 years) considered as control group. The four SNPs genotypes were not
associated with CAD or myocardial infarction (MI) in our population. No difference in haplotype distributions was detected between CAD cases and controls (P= 0.25).
No evidence for association of haplotype B (HapB) with CAD or MI was found
(OR= 0.8, P= 0.25 ; OR= 0.9, P= 0.54, respectively). In conclusion, haplotype B of
ALOX5AP gene is not associated with increased risk for CAD in the Lebanese
population. Our findings dispute the assumption that ALOX5AP is a susceptibility
gene for CAD and may limit the applicability of FLAP antagonists in prophylaxis of
CAD.