Association of ALOX5AP haplotypes with susceptibility to coronary artery disease in a Chinese Han population.

ABSTRACT

BACKGROUND: The 5-lipoxygenase activating protein (FLAP), encoded by the activating 5-lipoxygenase (ALOX5AP) gene, is a crucial mediator of the biosynthesis of leukotrienes, which have been implicated in atherosclerosis. This study investigates whether ALOX5AP polymorphisms are associated with coronary artery disease (CAD) in a Chinese Han population. METHODS: The promoter, exons, splice site region and 3'-untranslated region of the ALOX5AP gene were sequenced in 48 subjects. Three polymorphic sites (-1340T/G, +8733T/C, +20616G/C) found through sequencing were evaluated in 656 patients with angiographically proven CAD and 678 controls with normal coronary angiograms using a polymerase chain reaction and restriction fragment length polymorphism assay. Allelic, genotypic linkage disequilibrium and haplotypic association testing were performed using SHEsis and LDA software. Binary logistic regression was used to control for the presence of vascular risk factors. RESULTS: Seven single nucleotide polymorphisms (SNPs) were found through screening. No significant differences in allele carriers and genotype frequencies of the ALOX5AP polymorphisms were observed between the two groups. However, when the results of the three SNPs were combined, there was a significant association between two of the haplotypes and the risk of CAD. The haplotype GCG had a significantly greater frequency in patients than in controls (P<0.001, OR=1.728, 95%CI=1.375-2.171), and the frequency of haplotype TCG was higher in controls (P<0.001, OR=0.623, 95%CI=0.519-0.748). CONCLUSION: The data indicate that ALOX5AP gene variation is a genetic factor associated with interindividual differences in CAD risk.